Skip to main content
SpringerLink
Log in

Growth differentiation factor 15 (GDF-15) in endocrinology

  • Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Human growth differentiation factor 15 (GDF-15) is a widely distributed protein that has shown to play multiple roles in both physiological and pathological conditions. In healthy individuals, GDF-15 is mainly expressed in the placenta, followed by the prostate, although low levels of expression have also been detected in different organs. GDF-15 acts through a recently identified receptor called glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) which signals through the rearranged during transfection (RET) tyrosine kinase receptor. The effects of GDF-15 are pleiotropic and include appetite regulation, and actions on metabolism, pregnancy, cell survival, immune response, and inflammation. GDF-15 also plays different roles in the pathophysiology of cardiovascular disease, autoimmunity, cancer-associated anorexia/cachexia, and diabetes. In recent years, several studies have reported a link between GDF-15 and the endocrine system. In this review, we up-date and summarize the relevant investigations of the relationships between GDF-15 and different endocrine conditions. We also assess the potential pathogenic role and potential therapeutic applications of GDF-15 in the field of endocrinology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. M.R. Bootcov, A.R. Bauskin, S.M. Valenzuela, A.G. Moore, M. Bansal, X.Y. He, H.P. Zhang, M. Donnellan, S. Mahler, K. Pryor, B.J. Walsh, R.C. Nicholson, W.D. Fairlie, S.B. Por, J.M. Robbins, S.N. Breit, MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc. Natl. Acad. Sci. USA. 94, 11514–11519 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. R. Hromas, M. Hufford, J. Sutton, D. Xu, Y. Li, L. Lu, PLAB, a novel placental bone morphogenetic protein. Biochim. Biophys. Acta. 1354, 40–44 (1997)

    Article  CAS  PubMed  Google Scholar 

  3. L.N. Lawton, M.F. Bonaldo, P.C. Jelenc, L. Qiu, S.A. Baumes, R.A. Marcelino, G.M. de Jesus, S. Wellington, J.A. Knowles, D. Warburton, S. Brown, M.B. Soares, Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta. Gene. 203, 17–26 (1997)

    Article  CAS  PubMed  Google Scholar 

  4. S.M. Lockhart, V. Saudek, S. O’Rahilly, GDF15: A Hormone Conveying Somatic Distress to the Brain. Endocr. Rev. 41, bnaa007 (2020). https://doi.org/10.1210/endrev/bnaa007

    Article  PubMed  PubMed Central  Google Scholar 

  5. A. Assadi, A. Zahabi, R.A. Hart, GDF15, an update of the physiological and pathological roles it plays: a review. Pflugers Arch. 472, 1535–1546 (2020)

    Article  CAS  PubMed  Google Scholar 

  6. S.J. Baek, T. Eling, Growth differentiation factor 15 (GDF15): A survival protein with therapeutic potential in metabolic diseases. Pharmacol. Ther. 198, 46–58 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. W.D. Fairlie, A.G. Moore, A.R. Bauskin, P.K. Russell, H.P. Zhang, S.N. Breit, MIC-1 is a novel TGF-beta superfamily cytokine associated with macrophage activation. J. Leukoc. Biol. 65, 2–5 (1999)

    Article  CAS  PubMed  Google Scholar 

  8. M. Uhlén, L. Fagerberg, B.M. Hallström, C. Lindskog, P. Oksvold, A. Mardinoglu, Å. Sivertsson, C. Kampf, E. Sjöstedt, A. Asplund, I. Olsson, K. Edlund, E. Lundberg, S. Navani, C.A. Szigyarto, J. Odeberg, D. Djureinovic, J.O. Takanen, S. Hober, T. Alm, P.H. Edqvist, H. Berling, H. Tegel, J. Mulder, J. Rockberg, P. Nilsson, J.M. Schwenk, M. Hamsten, K. von Feilitzen, M. Forsberg, L. Persson, F. Johansson, M. Zwahlen, G. von Heijne, J. Nielsen, F. Pontén, Proteomics. Tissue-based map of the human proteome. Science 347, 1260419 (2015)

    Article  PubMed  Google Scholar 

  9. V.W.W. Tsai, Y. Husaini, A. Sainsbury, D.A. Brown, S.N. Breit, The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases. Cell. Metab. 28, 353–368 (2018)

    Article  CAS  PubMed  Google Scholar 

  10. T.A. Zimmers, X. Jin, E.C. Hsiao, S.A. McGrath, A.F. Esquela, L.G. Koniaris, Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury. Shock. 23, 543–548 (2005)

    CAS  PubMed  Google Scholar 

  11. T.A. Zimmers, X. Jin, E.C. Hsiao, E.A. Perez, R.H. Pierce, K.D. Chavin, L.G. Koniaris, Growth differentiation factor-15: induction in liver injury through p53 and tumor necrosis factor-independent mechanisms. J. Surg. Res. 130, 45–51 (2006)

    Article  CAS  PubMed  Google Scholar 

  12. T. Kempf, M. Eden, J. Strelau, M. Naguib, C. Willenbockel, J. Tongers, J. Heineke, D. Kotlarz, J. Xu, J.D. Molkentin, H.W. Niessen, H. Drexler, K.C. Wollert, The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circ. Res. 98, 351–360 (2006)

    Article  CAS  PubMed  Google Scholar 

  13. H.T. Liu, H.C. Wang, L. Tao, C.X. Li, F. Li, Y.Y. Zhang, B.W. Liu, Stress-induced growth-differentiation factor 15 plays an intriguing role in cardiovascular diseases. Chin. Med. J. (Engl). 126, 1350–1354 (2013)

    PubMed  Google Scholar 

  14. J. Wischhusen, I. Melero, W.H. Fridman, Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint. Front. Immunol. 11, 951 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. R. Adela, S.K. Banerjee, GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective. J. Diabetes Res. 2015, 490842 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  16. M. Arkoumani, N. Papadopoulou-Marketou, N.C. Nicolaides, C. Kanaka-Gantenbein, N. Tentolouris, I. Papassotiriou, The clinical impact of growth differentiation factor-15 in heart disease: A 2019 update. Crit. Rev. Clin. Lab. Sci. 57, 114–125 (2020)

    Article  CAS  PubMed  Google Scholar 

  17. A.C. Eddy, A.J. Trask, Growth differentiation factor-15 and its role in diabetes and cardiovascular disease. Cytokine Growth Factor Rev. 57, 11–18 (2021)

    Article  CAS  PubMed  Google Scholar 

  18. S.H. Lee, J.Y. Lee, K. Lim, Y. Lee, J. Koh, Associations Between Plasma Growth and Differentiation Factor-15 with Aging Phenotypes in Muscle, Adipose Tissue, and Bone. Calcif. Tissue Int. 110, 236–243 (2022)

    Article  CAS  PubMed  Google Scholar 

  19. H. Liu, Y. Huang, Y. Lyu, W. Dai, Y. Tong, Y. Li, GDF15 as a biomarker of ageing. Exp. Gerontol. 146, 111228 (2021)

    Article  CAS  PubMed  Google Scholar 

  20. H. Johnen, S. Lin, T. Kuffner, D.A. Brown, V.W. Tsai, A.R. Bauskin, L. Wu, G. Pankhurst, L. Jiang, S. Junankar, M. Hunter, W.D. Fairlie, N.J. Lee, R.F. Enriquez, P.A. Baldock, E. Corey, F.S. Apple, M.M. Murakami, E. Lin, C. Wang, M.J. During, A. Sainsbury, H. Herzog, S.N. Breit, Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1. Nat. Med. 13, 1333–1340 (2007)

    Article  CAS  PubMed  Google Scholar 

  21. V.W. Tsai, L. Macia, H. Johnen, T. Kuffner, R. Manadhar, S.B. Jørgensen, K.K.M. Lee-Ng, H.P. Zhang, L. Wu, C.P. Marquis, L. Jiang, Y. Husaini, S. Lin, H. Herzog, D.A. Brown, A. Sainsbury, S.N. Breit, TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator. PLoS ONE 8, e55174 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. T. Borner, H.S. Wald, M.Y. Ghidewon, B. Zhang, Z. Wu, B.C. De Jonghe, D. Breen, H.J. Grill, GDF15 Induces an Aversive Visceral Malaise State that Drives Anorexia and Weight Loss. Cell. Rep. 31, 107543 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. M. Ghidewon, H.S. Wald, A.D. McKnight, B.C. De Jonghe, D.M. Breen, A.L. Alhadeff, T. Borner, H.J. Grill, Growth differentiation factor 15 (GDF15) and semaglutide inhibit food intake and body weight through largely distinct, additive mechanisms. Diabetes Obes. Metab. 24, 1010–1020 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. M. Uhlen, C. Zhang, S. Lee, E. Sjöstedt, L. Fagerberg, G. Bidkhori, R. Benfeitas, M. Arif, Z. Liu, F. Edfors, K. Sanli, K. von Feilitzen, P. Oksvold, E. Lundberg, S. Hober, P. Nilsson, J. Mattsson, J.M. Schwenk, H. Brunnström, B. Glimelius, T. Sjöblom, P. Edqvist, D. Djureinovic, P. Micke, C. Lindskog, A. Mardinoglu, F. Ponten, A pathology atlas of the human cancer transcriptome. Science. 357, eaan2507 (2017). https://doi.org/10.1126/science.aan2507

    Article  CAS  PubMed  Google Scholar 

  25. T.E. Eling, S.J. Baek, M. Shim, C.H. Lee, NSAID activated gene (NAG-1), a modulator of tumorigenesis. J. Biochem. Mol. Biol. 39, 649–655 (2006)

    CAS  PubMed  Google Scholar 

  26. A.G. Moore, D.A. Brown, W.D. Fairlie, A.R. Bauskin, P.K. Brown, M.L. Munier, P.K. Russell, L.A. Salamonsen, E.M. Wallace, S.N. Breit, The transforming growth factor-ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women. J. Clin. Endocrinol. Metab. 85, 4781–4788 (2000)

    CAS  PubMed  Google Scholar 

  27. T.M. Michelsen, T. Henriksen, D. Reinhold, T.L. Powell, T. Jansson, The human placental proteome secreted into the maternal and fetal circulations in normal pregnancy based on 4-vessel sampling. Faseb J. 33, 2944–2956 (2019)

    Article  CAS  PubMed  Google Scholar 

  28. U. Andersson-Hall, L. Joelsson, P. Svedin, C. Mallard, A. Holmäng, Growth-differentiation-factor 15 levels in obese and healthy pregnancies: Relation to insulin resistance and insulin secretory function. Clin. Endocrinol. (Oxf). 95, 92–100 (2021)

    Article  CAS  PubMed  Google Scholar 

  29. S.N. Breit, H. Johnen, A.D. Cook, V.W. Tsai, M.G. Mohammad, T. Kuffner, H.P. Zhang, C.P. Marquis, L. Jiang, G. Lockwood, M. Lee-Ng, Y. Husaini, L. Wu, J.A. Hamilton, D.A. Brown, The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism. Growth Factors 29, 187–195 (2011)

    Article  CAS  PubMed  Google Scholar 

  30. K. Unsicker, B. Spittau, K. Krieglstein, The multiple facets of the TGF-β family cytokine growth/differentiation factor-15/macrophage inhibitory cytokine-1. Cytokine Growth Factor Rev. 24, 373–384 (2013)

    Article  CAS  PubMed  Google Scholar 

  31. J.A. Siddiqui, P. Seshacharyulu, S. Muniyan, R. Pothuraju, P. Khan, R. Vengoji, S. Chaudhary, S.K. Maurya, S.M. Lele, M. Jain, K. Datta, M.W. Nasser, S.K. Batra, GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation. Bone Res. 10, 6-021–00178-6 (2022)

    Article  Google Scholar 

  32. J.J. Li, J. Liu, K. Lupino, X. Liu, L. Zhang, L. Pei, Growth Differentiation Factor 15 Maturation Requires Proteolytic Cleavage by PCSK3, -5, and -6. Mol. Cell. Biol. 38, e00249–18 (2018). https://doi.org/10.1128/MCB.00249-18. Print 2018 Nov 1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. L. Rochette, M. Zeller, Y. Cottin, C. Vergely, Insights Into Mechanisms of GDF15 and Receptor GFRAL: Therapeutic Targets. Trends Endocrinol. Metab. 31, 939–951 (2020)

    Article  CAS  PubMed  Google Scholar 

  34. Y. Xiong, K. Walker, X. Min, C. Hale, T. Tran, R. Komorowski, J. Yang, J. Davda, N. Nuanmanee, D. Kemp, X. Wang, H. Liu, S. Miller, K.J. Lee, Z. Wang, M.M. Véniant, Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys. Sci. Transl. Med. 9, eaan8732 (2017). https://doi.org/10.1126/scitranslmed.aan8732

    Article  CAS  PubMed  Google Scholar 

  35. A.R. Bauskin, L. Jiang, X.W. Luo, L. Wu, D.A. Brown, S.N. Breit, The TGF-beta superfamily cytokine MIC-1/GDF15: secretory mechanisms facilitate creation of latent stromal stores. J. Interferon. Cytokine Res. 30, 389–397 (2010)

    Article  CAS  PubMed  Google Scholar 

  36. S.J. Baek, J. Kim, J.B. Nixon, R.P. DiAugustine, T.E. Eling, Expression of NAG-1, a transforming growth factor-beta superfamily member, by troglitazone requires the early growth response gene EGR-1. J. Biol. Chem. 279, 6883–6892 (2004)

    Article  CAS  PubMed  Google Scholar 

  37. K. Tsui, S. Hsu, L. Chung, Y. Lin, T. Feng, T. Lee, P. Chang, H. Juang, Growth differentiation factor-15: a p53- and demethylation-upregulating gene represses cell proliferation, invasion, and tumorigenesis in bladder carcinoma cells. Sci. Rep. 5, 12870 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. S.N. Breit, D.A. Brown, V.W. Tsai, The GDF15-GFRAL Pathway in Health and Metabolic Disease: Friend or Foe? Annu. Rev. Physiol. 83, 127–151 (2021)

    Article  CAS  PubMed  Google Scholar 

  39. N.S. Anderson, C.M. Haynes, Folding the Mitochondrial UPR into the Integrated Stress Response. Trends Cell Biol. 30, 428–439 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. L.K. Townsend, A.J. Weber, E.A. Day, H. Shamshoum, S.J. Shaw, C.G.R. Perry, B.E. Kemp, G.R. Steinberg, D.C. Wright, AMPK mediates energetic stress-induced liver GDF15. Faseb J. 35, e21218 (2021)

    Article  CAS  PubMed  Google Scholar 

  41. P.J. Emmerson, F. Wang, Y. Du, Q. Liu, R.T. Pickard, M.D. Gonciarz, T. Coskun, M.J. Hamang, D.K. Sindelar, K.K. Ballman, L.A. Foltz, A. Muppidi, J. Alsina-Fernandez, G.C. Barnard, J.X. Tang, X. Liu, X. Mao, R. Siegel, J.H. Sloan, P.J. Mitchell, B.B. Zhang, R.E. Gimeno, B. Shan, X. Wu, The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL. Nat. Med. 23, 1215–1219 (2017)

    Article  CAS  PubMed  Google Scholar 

  42. L. Yang, C. Chang, Z. Sun, D. Madsen, H. Zhu, S.B. Padkjær, X. Wu, T. Huang, K. Hultman, S.J. Paulsen, J. Wang, A. Bugge, J.B. Frantzen, P. Nørgaard, J.F. Jeppesen, Z. Yang, A. Secher, H. Chen, X. Li, L.M. John, B. Shan, Z. He, X. Gao, J. Su, K.T. Hansen, W. Yang, S.B. Jørgensen, GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand. Nat. Med. 23, 1158–1166 (2017)

    Article  CAS  PubMed  Google Scholar 

  43. J. Hsu, S. Crawley, M. Chen, D.A. Ayupova, D.A. Lindhout, J. Higbee, A. Kutach, W. Joo, Z. Gao, D. Fu, C. To, K. Mondal, B. Li, A. Kekatpure, M. Wang, T. Laird, G. Horner, J. Chan, M. McEntee, M. Lopez, D. Lakshminarasimhan, A. White, S. Wang, J. Yao, J. Yie, H. Matern, M. Solloway, R. Haldankar, T. Parsons, J. Tang, W.D. Shen, Y. Alice Chen, H. Tian, B.B. Allan, Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15. Nature. 550, 255–259 (2017)

    Article  PubMed  Google Scholar 

  44. S.E. Mullican, X. Lin-Schmidt, C. Chin, J.A. Chavez, J.L. Furman, A.A. Armstrong, S.C. Beck, V.J. South, T.Q. Dinh, T.D. Cash-Mason, C.R. Cavanaugh, S. Nelson, C. Huang, M.J. Hunter, S.M. Rangwala, GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates. Nat. Med. 23, 1150–1157 (2017)

    Article  CAS  PubMed  Google Scholar 

  45. A. Wong, S. Bogni, P. Kotka, E. de Graaff, V. D’Agati, F. Costantini, V. Pachnis, Phosphotyrosine 1062 is critical for the in vivo activity of the Ret9 receptor tyrosine kinase isoform. Mol. Cell. Biol. 25, 9661–9673 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. A. Artz, S. Butz, D. Vestweber, GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-βRII heterodimer. Blood. 128, 529–541 (2016)

    Article  CAS  PubMed  Google Scholar 

  47. Y. Zhang, G. Zhang, Y. Liu, R. Chen, D. Zhao, V. McAlister, T. Mele, K. Liu, X. Zheng, GDF15 Regulates Malat-1 Circular RNA and Inactivates NFκB Signaling Leading to Immune Tolerogenic DCs for Preventing Alloimmune Rejection in Heart Transplantation. Front. Immunol. 9, 2407 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  48. A.A. Worth, R. Shoop, K. Tye, C.H. Feetham, G. D’Agostino, G.T. Dodd, F. Reimann, F.M. Gribble, E.C. Beebe, J.D. Dunbar, J.T. Alexander-Chacko, D.K. Sindelar, T. Coskun, P.J. Emmerson, S.M. Luckman, The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling. Elife. 9, https://doi.org/10.7554/eLife.55164 (2020)

  49. R.J. Whitson, M.S. Lucia, J.R. Lambert, Growth differentiation factor-15 (GDF-15) suppresses in vitro angiogenesis through a novel interaction with connective tissue growth factor (CCN2). J. Cell. Biochem. 114, 1424–1433 (2013)

    Article  CAS  PubMed  Google Scholar 

  50. T. Kempf, R. Horn-Wichmann, G. Brabant, T. Peter, T. Allhoff, G. Klein, H. Drexler, N. Johnston, L. Wallentin, K.C. Wollert, Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin. Chem. 53, 284–291 (2007)

    Article  CAS  PubMed  Google Scholar 

  51. S.Q. Khan, K. Ng, O. Dhillon, D. Kelly, P. Quinn, I.B. Squire, J.E. Davies, L.L. Ng, Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction. Eur. Heart J. 30, 1057–1065 (2009)

    Article  CAS  PubMed  Google Scholar 

  52. C. Andersson, D. Enserro, L. Sullivan, T.J. Wang, J.L.J. Januzzi, E.J. Benjamin, J.A. Vita, N.M. Hamburg, M.G. Larson, G.F. Mitchell, R.S. Vasan, Relations of circulating GDF-15, soluble ST2, and troponin-I concentrations with vascular function in the community: The Framingham Heart Study. Atherosclerosis. 248, 245–251 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. L. Wallentin, D. Lindholm, A. Siegbahn, L. Wernroth, R.C. Becker, C.P. Cannon, J.H. Cornel, A. Himmelmann, E. Giannitsis, R.A. Harrington, C. Held, S. Husted, H.A. Katus, K.W. Mahaffey, P.G. Steg, R.F. Storey, S.K. James; PLATO study group, Biomarkers in relation to the effects of ticagrelor in comparison with clopidogrel in non-ST-elevation acute coronary syndrome patients managed with or without in-hospital revascularization: a substudy from the Prospective Randomized Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation. 129, 293–303 (2014)

    Article  CAS  PubMed  Google Scholar 

  54. K.C. Wollert, T. Kempf, L. Wallentin, Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease. Clin. Chem. 63, 140–151 (2017)

    Article  CAS  PubMed  Google Scholar 

  55. A. Amstad, M. Coray, C. Frick, C. Barro, J. Oechtering, M. Amann, J. Wischhusen, L. Kappos, Y. Naegelin, J. Kuhle, M. Mehling, Growth differentiation factor 15 is increased in stable MS. Neurol. Neuroimmunol. Neuroinflamm. 7, e675 (2020). https://doi.org/10.1212/NXI.0000000000000675. Print 2020 Mar 5

  56. K.C. Wollert, T. Kempf, E. Giannitsis, T. Bertsch, S.L. Braun, H. Maier, M. Reim, R.H. Christenson, An Automated Assay for Growth Differentiation Factor 15. J. Appl. Lab. Med. 1, 510–521 (2017)

    Article  CAS  PubMed  Google Scholar 

  57. K. Souček, A. Malenovská, Z. Kahounová, J. Remšík, Z. Holubcová, T. Soukup, D. Kurfürstová, J. Bouchal, T. Suchánková, E. Slabáková, A. Hampl, Presence of growth/differentiation factor-15 cytokine in human follicular fluid, granulosa cells, and oocytes. J. Assist. Reprod. Genet. 35, 1407–1417 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  58. S. Tong, B. Marjono, D.A. Brown, S. Mulvey, S.N. Breit, U. Manuelpillai, E.M. Wallace, Serum concentrations of macrophage inhibitory cytokine 1 (MIC 1) as a predictor of miscarriage. Lancet. 363, 129–130 (2004)

    Article  CAS  PubMed  Google Scholar 

  59. S. Tong, G. Ngian, J.L. Onwude, M. Permezel, B. Saglam, S. Hay, J.C. Konje, T.H. Marczylo, G. Fleming, S.P. Walker, M. Lappas, Diagnostic accuracy of maternal serum macrophage inhibitory cytokine-1 and pregnancy-associated plasma protein-A at 6-10 weeks of gestation to predict miscarriage. Obstet. Gynecol. 119, 1000–1008 (2012)

    Article  CAS  PubMed  Google Scholar 

  60. T.J. Kaitu’u-Lino, K. Bambang, J. Onwude, R. Hiscock, J. Konje, S. Tong, Plasma MIC-1 and PAPP-a levels are decreased among women presenting to an early pregnancy assessment unit, have fetal viability confirmed but later miscarry. PLoS ONE 8, e72437 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  61. Q. Chen, Y. Wang, M. Zhao, J. Hyett, F. da Silva Costa, G. Nie, Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases. Cytokine. 83, 226–230 (2016)

    Article  CAS  PubMed  Google Scholar 

  62. M. Tang, M. Luo, W. Lu, S. Wang, R. Zhang, W. Liang, J. Gu, X. Yu, X. Zhang, C. Hu, Serum growth differentiation factor 15 is associated with glucose metabolism in the third trimester in Chinese pregnant women. Diabetes Res. Clin. Pract. 156, 107823 (2019)

    Article  CAS  PubMed  Google Scholar 

  63. S. Banerjee, R. Bhattacharjee, A. Sur, P. Adhikary, S. Chowdhury, A study of serum growth differentiation factor 15 in Indian women with and without gestational diabetes mellitus in the third trimester of pregnancy and its association with pro-inflammatory markers and glucose metabolism. Diabetol. Int. 12, 254–259 (2020)

    Article  PubMed  PubMed Central  Google Scholar 

  64. E. Li, P. Chen, J. Lu, J. Dai, J. Yi, S. Zhang, H. Jin, M. Guo, H. Wang, X. Yu, Serum growth differentiation factor 15 is closely associated with metabolic abnormalities in Chinese pregnant women. J. Diabetes Investig. 12, 1501–1507 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Y. Lu, S. Liu, Y. Zhang, F. Liang, X. Zhu, Y. Xiao, J. Wang, C. Ding, S. Banerjee, J. Yin, Q. Ma, Association between growth differentiation factor 15 levels and gestational diabetes mellitus: A combined analysis. Front. Endocrinol. (Lausanne). 14, 1084896 (2023)

    Article  PubMed  PubMed Central  Google Scholar 

  66. S.N. Breit, V.W. Tsai, D.A. Brown, Targeting Obesity and Cachexia: Identification of the GFRAL Receptor-MIC-1/GDF15 Pathway. Trends Mol. Med. 23, 1065–1067 (2017)

    Article  CAS  PubMed  Google Scholar 

  67. A.R. Bauskin, D.A. Brown, T. Kuffner, H. Johnen, X.W. Luo, M. Hunter, S.N. Breit, Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer. Cancer Res. 66, 4983–4986 (2006)

    Article  CAS  PubMed  Google Scholar 

  68. T. Borner, M. Arnold, J. Ruud, S.N. Breit, W. Langhans, T.A. Lutz, A. Blomqvist, T. Riediger, Anorexia-cachexia syndrome in hepatoma tumour-bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC-1/GDF15. J. Cachexia Sarcopenia Muscle 8, 417–427 (2017)

    Article  PubMed  Google Scholar 

  69. V.W. Tsai, L. Macia, C. Feinle-Bisset, R. Manandhar, A. Astrup, A. Raben, J.K. Lorenzen, P.T. Schmidt, F. Wiklund, N.L. Pedersen, L. Campbell, A. Kriketos, A. Xu, Z. Pengcheng, W. Jia, P.M.G. Curmi, C.N. Angstmann, K.K.M. Lee-Ng, H.P. Zhang, C.P. Marquis, Y. Husaini, C. Beglinger, S. Lin, H. Herzog, D.A. Brown, A. Sainsbury, S.N. Breit, Serum Levels of Human MIC-1/GDF15 Vary in a Diurnal Pattern, Do Not Display a Profile Suggestive of a Satiety Factor and Are Related to BMI. PLoS ONE 10, e0133362 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  70. M. Karczewska-Kupczewska, I. Kowalska, A. Nikolajuk, A. Adamska, E. Otziomek, M. Gorska, M. Straczkowski, Hyperinsulinemia acutely increases serum macrophage inhibitory cytokine-1 concentration in anorexia nervosa and obesity. Clin. Endocrinol. (Oxf) 76, 46–50 (2012)

    Article  CAS  PubMed  Google Scholar 

  71. M.H. Schernthaner-Reiter, D. Kasses, C. Tugendsam, M. Riedl, S. Peric, G. Prager, M. Krebs, M. Promintzer-Schifferl, M. Clodi, A. Luger, G. Vila, Growth differentiation factor 15 increases following oral glucose ingestion: effect of meal composition and obesity. Eur. J. Endocrinol. 175, 623–631 (2016)

    Article  CAS  PubMed  Google Scholar 

  72. L. Macia, V.W. Tsai, A.D. Nguyen, H. Johnen, T. Kuffner, Y.C. Shi, S. Lin, H. Herzog, D.A. Brown, S.N. Breit, A. Sainsbury, Macrophage inhibitory cytokine 1 (MIC-1/GDF15) decreases food intake, body weight and improves glucose tolerance in mice on normal & obesogenic diets. PLoS ONE 7, e34868 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. J. Li, L. Yang, W. Qin, G. Zhang, J. Yuan, F. Wang, Adaptive induction of growth differentiation factor 15 attenuates endothelial cell apoptosis in response to high glucose stimulus. PLoS ONE 8, e65549 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. E.S. Nakayasu, F. Syed, S.A. Tersey, M.A. Gritsenko, H.D. Mitchell, C.Y. Chan, E. Dirice, J.V. Turatsinze, Y. Cui, R.N. Kulkarni, D.L. Eizirik, W.J. Qian, B.M. Webb-Robertson, C. Evans-Molina, R.G. Mirmira, T.O. Metz, Comprehensive Proteomics Analysis of Stressed Human Islets Identifies GDF15 as a Target for Type 1 Diabetes Intervention. Cell. Metab. 31, 363–374.e6 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. S. Sarkar, J.T. Melchior, H.R. Henry, F. Syed, R.G. Mirmira, E.S. Nakayasu, T.O. Metz, GDF15: a potential therapeutic target for type 1 diabetes. Expert Opin. Ther. Targets. 26, 57–67 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. P. Lertpatipanpong, J. Lee, I. Kim, T. Eling, S.Y. Oh, J.K. Seong, S.J. Baek, The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice. Sci. Rep. 11, 15027-021–94581-y (2021)

    Article  Google Scholar 

  77. M. Asrih, R. Dusaulcy, Y. Gosmain, J. Philippe, E. Somm, F.R. Jornayvaz, B.E. Kang, Y. Jo, M.J. Choi, H.S. Yi, D. Ryu, K. Gariani, Growth differentiation factor-15 prevents glucotoxicity and connexin-36 downregulation in pancreatic beta-cells. Mol. Cell. Endocrinol. 541, 111503 (2022)

    Article  CAS  PubMed  Google Scholar 

  78. Y. Wang, J. Chen, T. Sang, C. Chen, H. Peng, X. Lin, Q. Zhao, S. Chen, T. Eling, X. Wang, NAG-1/GDF15 protects against streptozotocin-induced type 1 diabetes by inhibiting apoptosis, preserving beta-cell function, and suppressing inflammation in pancreatic islets. Mol. Cell. Endocrinol. 549, 111643 (2022)

    Article  CAS  PubMed  Google Scholar 

  79. M. Lajer, A. Jorsal, L. Tarnow, H.H. Parving, P. Rossing, Plasma growth differentiation factor-15 independently predicts all-cause and cardiovascular mortality as well as deterioration of kidney function in type 1 diabetic patients with nephropathy. Diabetes Care 33, 1567–1572 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. G. Vila, M. Riedl, C. Anderwald, M. Resl, A. Handisurya, M. Clodi, G. Prager, B. Ludvik, M. Krebs, A. Luger, The relationship between insulin resistance and the cardiovascular biomarker growth differentiation factor-15 in obese patients. Clin. Chem. 57, 309–316 (2011)

    Article  CAS  PubMed  Google Scholar 

  81. J.H. Hong, H.K. Chung, H.Y. Park, K. Joung, J.H. Lee, J.G. Jung, K.S. Kim, H.J. Kim, B.J. Ku, M. Shong, GDF15 Is a Novel Biomarker for Impaired Fasting Glucose. Diabetes Metab. J. 38, 472–479 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  82. X. Bao, Y. Borné, I.F. Muhammad, J. Nilsson, L. Lind, O. Melander, K. Niu, M. Orho-Melander, G. Engström, Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer-Cardiovascular Cohort. Diabetologia. 62, 78–86 (2019)

    Article  CAS  PubMed  Google Scholar 

  83. X. Wu, W. Xuan, L. You, H. Lian, F. Li, X. Zhang, Q. Chen, K. Sun, C. Chen, M. Xu, Y. Li, L. Yan, X. Zhang, M. Ren, Associations of GDF-15 and GDF-15/adiponectin ratio with odds of type 2 diabetes in the Chinese population. Endocrine. 72, 423–436 (2021)

    Article  CAS  PubMed  Google Scholar 

  84. A.C. Carlsson, C. Nowak, L. Lind, C.J. Östgren, F.H. Nyström, J. Sundström, J.J. Carrero, U. Riserus, E. Ingelsson, T. Fall, J. Ärnlöv, Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes: a proteomics approach. Ups. J. Med. Sci. 125, 37–43 (2020)

    Article  PubMed  Google Scholar 

  85. M.Y. Shin, J.M. Kim, Y.E. Kang, M.K. Kim, K.H. Joung, J.H. Lee, K.S. Kim, H.J. Kim, B.J. Ku, M. Shong, Association between Growth Differentiation Factor 15 (GDF15) and Cardiovascular Risk in Patients with Newly Diagnosed Type 2 Diabetes Mellitus. J. Korean Med. Sci. 31, 1413–1418 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. S. Xie, Q. Li, A.O.Y. Luk, H. Lan, P.K.S. Chan, A. Bayés-Genís, F.K.L. Chan, E. Fung, Major Adverse Cardiovascular Events and Mortality Prediction by Circulating GDF-15 in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Biomolecules 12, 934 (2022). https://doi.org/10.3390/biom12070934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. D.P. Jacobsen, R. Røysland, H. Strand, K. Moe, M. Sugulle, T. Omland, A.C. Staff, Cardiovascular biomarkers in pregnancy with diabetes and associations to glucose control. Acta Diabetol. 59, 1229–1236 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. M. Sugulle, R. Dechend, F. Herse, M.S. Weedon-Fekjaer, G.M. Johnsen, K.B. Brosnihan, L. Anton, F.C. Luft, K.C. Wollert, T. Kempf, A.C. Staff, Circulating and placental growth-differentiation factor 15 in preeclampsia and in pregnancy complicated by diabetes mellitus. Hypertension. 54, 106–112 (2009)

    Article  CAS  PubMed  Google Scholar 

  89. J. Zhao, M. Li, Y. Chen, S. Zhang, H. Ying, Z. Song, Y. Lu, X. Li, X. Xiong, J. Jiang, Elevated Serum Growth Differentiation Factor 15 Levels in Hyperthyroid Patients. Front. Endocrinol. (Lausanne). 9, 793 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  90. S. Salam, M. Abbas, Evaluation of Growth Differentiation Factor-15 in Non-Diabetic Hypothyroid Patients with Normal Insulin Sensitivity and Maintained on Oral Thyroxin Therapy. Int. J. Sci. Res. 6, 1056–1059 (2017)

    Google Scholar 

  91. D. Arslan, M. Buyukinan, C. Uysal, C.D. Deniz, Evaluation of cardiovascular risk by growth-differentiation factor-15 and tissue Doppler imaging in children with subclinical hypothyroidism. Endocrine. 65, 601–607 (2019)

    Article  CAS  PubMed  Google Scholar 

  92. H. Zhang, W. Zhang, X. Tu, Y. Niu, X. Li, L. Qin, Z. Yang, Q. Su, Elevated serum growth differentiation factor 15 levels are associated with thyroid nodules in type 2 diabetes aged over 60 years. Oncotarget. 8, 41379–41386 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  93. N.I. Zhiqiang, W. Yongheng, P. Shuwang, Y. Zhengtai, Expression of growth differentiation factor 15 in papillary thyroid carcinoma and its clinical significance. Cancer Res. Clinic 6, 282–286 (2021)

    Google Scholar 

  94. Y.E. Kang, J.M. Kim, M.A. Lim, S.E. Lee, S. Yi, J.T. Kim, C. Oh, L. Liu, Y. Jin, S. Jung, H. Won, J.W. Chang, J.H. Lee, H.J. Kim, H.Y. Koh, S. Jun, S.W. Cho, M. Shong, B.S. Koo, Growth Differentiation Factor 15 is a Cancer Cell-Induced Mitokine That Primes Thyroid Cancer Cells for Invasiveness. Thyroid. 31, 772–786 (2021)

    Article  CAS  PubMed  Google Scholar 

  95. S. Jeong, S.G. Lee, K.H. Kim, X. Zhu, W.K. Lee, H.Y. Lee, S. Park, M. Lee, S. Cheng, J. Lee, Y.S. Jo, Cell non-autonomous effect of hepatic growth differentiation factor 15 on the thyroid gland. Front. Endocrinol. (Lausanne). 13, 966644 (2022)

    Article  PubMed  PubMed Central  Google Scholar 

  96. X. Chen, R. Wang, T. Xu, Y. Zhang, H. Li, C. Du, K. Wang, Z. Gao, Identification of candidate genes associated with papillary thyroid carcinoma pathogenesis and progression by weighted gene co-expression network analysis. Transl. Cancer. Res. 10, 694–713 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. S.W. Hong, J. Kang, Growth differentiation factor-15 as a modulator of bone and muscle metabolism. Front. Endocrinol. (Lausanne). 13, 948176 (2022)

    Article  PubMed  PubMed Central  Google Scholar 

  98. E. Hinoi, H. Ochi, T. Takarada, E. Nakatani, T. Iezaki, H. Nakajima, H. Fujita, Y. Takahata, S. Hidano, T. Kobayashi, S. Takeda, Y. Yoneda, Positive regulation of osteoclastic differentiation by growth differentiation factor 15 upregulated in osteocytic cells under hypoxia. J. Bone Miner. Res. 27, 938–949 (2012)

    Article  CAS  PubMed  Google Scholar 

  99. M. Westhrin, S.H. Moen, T. Holien, A.K. Mylin, L. Heickendorff, O.E. Olsen, A. Sundan, I. Turesson, P. Gimsing, A. Waage, T. Standal, Growth differentiation factor 15 (GDF15) promotes osteoclast differentiation and inhibits osteoblast differentiation and high serum GDF15 levels are associated with multiple myeloma bone disease. Haematologica. 100, e511–4 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. W. Li, C. Li, X. Zhou, T. Jiang, L. Guo, H. Liu, Relationship between GDF15 level and bone metabolism in postmenopausal Chinese women. Gynecol. Endocrinol. 36, 714–717 (2020)

    Article  CAS  PubMed  Google Scholar 

  101. Y. Osawa, T. Tanaka, R.D. Semba, G. Fantoni, R. Moaddel, J. Candia, E.M. Simonsick, S. Bandinelli, L. Ferrucci, Plasma Growth and Differentiation Factor 15 Predict Longitudinal Changes in Bone Parameters in Women, but Not in Men. J. Gerontol. A Biol. Sci. Med. Sci. 77, 1951–1958 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. J. Windrichova, R. Fuchsova, R. Kucera, O. Topolcan, O. Fiala, J. Finek, D. Slipkova, MIC1/GDF15 as a Bone Metastatic Disease Biomarker. Anticancer Res. 37, 1501–1505 (2017)

    Article  PubMed  Google Scholar 

  103. S.M. Sadasivan, Y. Chen, N.S. Gupta, X. Han, K.R. Bobbitt, D.A. Chitale, S.R. Williamson, A.G. Rundle, D. Tang, B.A. Rybicki, The interplay of growth differentiation factor 15 (GDF15) expression and M2 macrophages during prostate carcinogenesis. Carcinogenesis. 41, 1074–1082 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. B.A. Rybicki, S.M. Sadasivan, Y. Chen, O. Kravtsov, W. Palangmonthip, K. Arora, N.S. Gupta, S. Williamson, K. Bobbitt, D.A. Chitale, D. Tang, A.G. Rundle, K.A. Iczkowski, Growth and differentiation factor 15 and NF-κB expression in benign prostatic biopsies and risk of subsequent prostate cancer detection. Cancer. Med. 10, 3013–3025 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. H. Liu, Y. Lyu, D. Li, Y. Cui, Y. Huang, W. Dai, Y. Li, Potential relation between soluble growth differentiation factor-15 and testosterone deficiency in male patients with coronary artery disease. Cardiovasc. Diabetol. 18, 21-019–0823-3 (2019)

    Article  Google Scholar 

  106. J. Chen, W. Dai, C. Zhu, H. Liu, Y. Li, P. Zhang, Circulating levels of growth differentiation factor 15 and sex hormones in male patients with HBV-associated hepatocellular carcinoma. Biomed. Pharmacother. 121, 109574 (2020)

    Article  CAS  PubMed  Google Scholar 

  107. T. Sun, R. Peng, X. Sun, Y. Li, Associations between Sex Hormones and Circulating Growth Differentiation Factor-15 in Male Patients with Major Depressive Disorder. Brain Sci. 11, 1612 (2021). https://doi.org/10.3390/brainsci11121612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Y. Mei, Y. Lyu, J. Le, D. Li, H. Liu, Z. Zhao, Y. Li, Raised circulating soluble growth differentiation factor 15 is negatively associated with testosterone level in hypogonadic men with type 2 diabetes. Diabetes Metab. Res. Rev. 38, e3564 (2022)

    Article  CAS  PubMed  Google Scholar 

  109. F. de Zegher, M. Díaz, J. Villarroya, M. Cairó, A. López-Bermejo, F. Villarroya, L. Ibáñez, The relative deficit of GDF15 in adolescent girls with PCOS can be changed into an abundance that reduces liver fat. Sci. Rep. 11, 7018-021–86317-9 (2021)

    Google Scholar 

  110. K. Kageyama, Y. Iwasaki, Y. Watanuki, S. Murasawa, K. Niioka, M. Tasso, A. Kosugi, M. Daimon, Growth differentiation factor-15 modulates adrenocorticotropic hormone synthesis in murine AtT-20 corticotroph cells. Peptides. 155, 170841 (2022)

    Article  CAS  PubMed  Google Scholar 

  111. Y. Hacıoğlu, M.E. Pişkinpaşa, P. Kılıçkaya, M. Niyazoğlu, B. Hacıoğlu, E. Hatipoğlu, Increased Serum Growth Differentiation Factor 15 Levels may be Associated with Diastolic Dysfunction in Acromegaly. Istanbul Med. J. 23, 179–182 (2022)

    Article  Google Scholar 

  112. X. Wu, Y. Wang, Z. Ren, L. Li, W. Qian, Y. Chen, W. Ren, Association between Growth Differentiation Factor-15 and Risk of Cardiovascular Diseases in Patients with Adult Growth Hormone Deficiency. Int. J. Endocrinol. 2021, 5921863 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  113. I. Cimino, H. Kim, Y.C.L. Tung, K. Pedersen, D. Rimmington, J.A. Tadross, S.N. Kohnke, A. Neves-Costa, A. Barros, S. Joaquim, D. Bennett, A. Melvin, S.M. Lockhart, A.J. Rostron, J. Scott, H. Liu, K. Burling, P. Barker, M.R. Clatworthy, E. Lee, A.J. Simpson, G.S.H. Yeo, L.F. Moita, K.K. Bence, S.B. Jørgensen, A.P. Coll, D.M. Breen, S. O’Rahilly, Activation of the hypothalamic-pituitary-adrenal axis by exogenous and endogenous GDF15. Proc. Natl. Acad. Sci. USA. 118, e2106868118 (2021). https://doi.org/10.1073/pnas.2106868118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. A. Melvin, D. Chantzichristos, C.J. Kyle, S.D. Mackenzie, B.R. Walker, G. Johannsson, R.H. Stimson, S. O’Rahilly, GDF15 Is Elevated in Conditions of Glucocorticoid Deficiency and Is Modulated by Glucocorticoid Replacement. J. Clin. Endocrinol. Metab. 105, 1427–1434 (2020)

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain

    Pedro Iglesias & Juan J. Díez

  2. Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain

    Pedro Iglesias & Juan J. Díez

  3. Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Majadahonda, Madrid, Spain

    Pedro Iglesias, Ramona A. Silvestre & Juan J. Díez

  4. Department of Clinical Biochemistry, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain

    Ramona A. Silvestre

  5. Department of Physiology, Medical School, Universidad Autónoma de Madrid, Madrid, Spain

    Ramona A. Silvestre

Authors
  1. Pedro Iglesias
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ramona A. Silvestre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juan J. Díez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pedro Iglesias.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Iglesias, P., Silvestre, R.A. & Díez, J.J. Growth differentiation factor 15 (GDF-15) in endocrinology. Endocrine 81, 419–431 (2023). https://doi.org/10.1007/s12020-023-03377-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-023-03377-9

Keywords

Search

Navigation