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Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23
Abstract
The endocrine fibroblast growth factors (FGFs), FGF19, FGF21 and FGF23, are critical for maintaining whole-body homeostasis, with roles in bile acid, glucose and lipid metabolism, modulation of vitamin D and phosphate homeostasis and metabolic adaptation during fasting. Given these functions, the endocrine FGFs have therapeutic potential in a wide array of chronic human diseases, including obesity, type 2 diabetes, cancer, and kidney and cardiovascular disease. However, the safety and feasibility of chronic endocrine FGF administration has been challenged, and FGF analogues and mimetics are now being investigated. Here, we discuss current knowledge of the complex biology of the endocrine FGFs and assess how this may be harnessed therapeutically.
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“As such, it is an important therapeutic target of protection against muscle and liver insulin resistance induced by lipids and DM2 [106,107].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [106]
In the citing paper
“Substances that act as adipokines, myokines, and hepatokines, such as FGF21, are essential for controlling glucose and lipid metabolism.”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [106]
Citations
Cites
Ahmed, A., Jorna, T., & Bhandari, S. (2016) · The Nephron journals/Nephron journals · doi:10.1159/000447068 · Cited by 11,782
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
FGF-21 as a novel metabolic regulator
Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23606 · Cited by 2,125
FGF23 induces left ventricular hypertrophy
Faul, C., Amaral, A. P., Oskouei, B., Hu, M.-C., Sloan, A., Isakova, T., Gutiérrez, O. M., Aguillon-Prada, R., Lincoln, J., Hare, J. M., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46122 · Cited by 2,027
PPARγ signaling and metabolism: the good, the bad and the future
Ahmadian, M., Suh, J. M., Hah, N., Liddle, C., Atkins, A. R., Downes, M., & Evans, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3159 · Cited by 2,016
The FGF family: biology, pathophysiology and therapy
Beenken, A., & Mohammadi, M. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2792 · Cited by 1,945
FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis
Shimada, T., Hasegawa, H., Yamazaki, Y., Muto, T., Hino, R., Takeuchi, Y., Fujita, T., Nakahara, K., Fukumoto, S., & Yamashita, T. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.0301264 · Cited by 1,883
Receptor Specificity of the Fibroblast Growth Factor Family
Ornitz, D. M., Xu, J., Colvin, J. S., McEwen, D. G., MacArthur, C. A., Coulier, F., Gao, G., & Goldfarb, M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.15292 · Cited by 1,871
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.001 · Cited by 1,865
Klotho converts canonical FGF receptor into a specific receptor for FGF23
Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S., & Yamashita, T. (2006) · Nature · doi:10.1038/nature05315 · Cited by 1,865
Research works printed but not linked: 1
- Mirza, M. A. et al. Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol. Dial. Transplant 24, 3125–3131 (2009). · DOI
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Puchalska, P., & Crawford, P. A. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.022 · Cited by 1,682
“, 2016), therapies that increase hepatic ketogenesis could prove salutary (Degirolamo et al., 2016; Honda et al., 2016).”
BackgroundFGF/FGFR signaling in health and disease
Xie, Y., Su, N., Yang, J., Tan, Q., Huang, S., Jin, M., Ni, Z., Zhang, B., Zhang, D., Luo, F., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00222-7 · Cited by 904
“Endocrine FGFs, encoded by FGF19 subfamily gene, which bind and activate FGFRs with the Klotho family protein, regulate a wide range of metabolic processes.(692) Based on the structure–function principle, separating mitogenic and metabolic activities of FGF19 through mutagenesis of five N-terminal and heparin-binding…”
BackgroundAdvances and challenges in targeting FGFR signalling in cancer
Babina, I. S., & Turner, N. C. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.8 · Cited by 820
Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases
Samuel, V. T., & Shulman, G. I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.002 · Cited by 745
“Increases in visceral adipose tissue (VAT) have been associated with dyslipidemia (Després et al., 1990), insulin resistance (Couillard et al.”
Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance
Meex, R. C. R., & Watt, M. J. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.56 · Cited by 631
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Geng, L., Lam, K. S. L., & Xu, A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0386-0 · Cited by 607
Yahagi, K., Kolodgie, F. D., Lutter, C., Mori, H., Romero, M. E., Finn, A. V., & Virmani, R. (2017) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.116.306256 · Cited by 573
Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus
Ferguson, D., & Finck, B. N. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00507-z · Cited by 520
Bile acid metabolism and signaling, the microbiota, and metabolic disease
Cai, J., Rimal, B., Jiang, C., Chiang, J. Y. L., & Patterson, A. D. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108238 · Cited by 529
Bile Acids as Metabolic Regulators and Nutrient Sensors
Chiang, J. Y. L., & Ferrell, J. M. (2019) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082018-124344 · Cited by 456
“However, FGF21 may potentially be utilized as a therapeutic to treat obesity and metabolic disease (21, 37, 130).”
BackgroundHarrison, S. A., Rinella, M. E., Abdelmalek, M. F., Trotter, J. F., Paredes, A. H., Arnold, H. L., Kugelmas, M., Bashir, M. R., Jaros, M. J., Ling, L., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30474-4 · Cited by 425
FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review)
Katoh, M. (2016) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2016.2620 · Cited by 407
“FGF23 is upregulated by serum phosphate, vitamin D and parathyroid hormone in bone to trans-duce endocrine signaling through FGFR1 and α -Klotho in the kidneys and negative feedback signaling through FGFR3 and α -Klotho in the parathyroid gland (118).”
Gu, Y., Wang, X., Li, J., Zhang, Y., Zhong, H., Liu, R., Zhang, D., Feng, Q., Xie, X., Hong, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01682-2 · Cited by 402
Goyal, L., Shi, L., Liu, L. Y., de la Cruz, F. F., Lennerz, J. K., Raghavan, S., Leschiner, I., Elagina, L., Siravegna, G., Ng, R. W. S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0182 · Cited by 384
“Hyperphosphatemia is a class effect of FGFR inhibitors arising from on-target pathway blockade of FGF23– FGFR1 signaling in the renal tubule (22, 36).”
BackgroundMazzaferro, V., El‐Rayes, B. F., Busset, M. D. D., Cotsoglou, C., Harris, W. P., Damjanov, N., Masi, G., Rimassa, L., Personeni, N., Braiteh, F., et al. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0334-0 · Cited by 366
The Role of Fibroblast Growth Factor (FGF) Signaling in Tissue Repair and Regeneration
Farooq, M., Khan, A. W., Kim, M. S., & Choi, S. (2021) · Cells · doi:10.3390/cells10113242 · Cited by 387
“FGF23, aside from being a phosphaturic hormone, serves as an important regulator of calcium and sodium reabsorption in the kidney [69].”
BackgroundTargeting the alternative bile acid synthetic pathway for metabolic diseases
Jia, W. P., Wei, M., Rajani, C., & Zheng, X. (2020) · Protein & Cell · doi:10.1007/s13238-020-00804-9 · Cited by 330
Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors
Dai, S., Zhou, Z. M., Chen, Z., Xu, G., & Chen, Y. (2019) · Cells · doi:10.3390/cells8060614 · Cited by 303
“Although nonselective inhibitors might be clinically beneficial and achieve therapeutic success to some extent, the development of those inhibitors has been restricted due to the undesirable off-target toxicities [80,81].”
BackgroundBile acid signaling pathways from the enterohepatic circulation to the central nervous system
Mertens, K. L., Kalsbeek, A., Soeters, M. R., & Eggink, H. M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00617 · Cited by 287
“In addition, it should be studied to which extend the different FGFs contribute to the FGFRs signaling in the CNS, because FGF21 binds to the same FGFR and β-Klotho complexes as FGF19 and generates similar effects when administered in the brain (Owen et al., 2015; Degirolamo et al., 2016).”
BackgroundHarrison, S. A., Neff, G., Guy, C. D., Bashir, M. R., Paredes, A. H., Frias, J. P., Younes, Z., Trotter, J. F., Gunn, N. T., Moussa, S. E., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.08.004 · Cited by 280
The Ever-Expanding Myokinome: Discovery Challenges and Therapeutic Implications
Whitham, M., & Febbraio, M. A. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.153 · Cited by 279
Kim, R. D., Sarker, D., Meyer, T., Yau, T. C. C., Macarulla, T. M., Park, J., Choo, S. P., Hollebecque, A., Sung, M. W., Lim, H.-Y., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0555 · Cited by 276
“FGFR4 pathway activation by FGF19 promotes bile acid production from cholesterol (24).”
BackgroundFibroblast Growth Factor 21—Metabolic Role in Mice and Men
Staiger, H., Keuper, M., Berti, L., Hrabě de Angelis, M., & Häring, H.-U. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00016 · Cited by 270
Harrison, S. A., Rossi, S. J., Paredes, A. H., Trotter, J. F., Bashir, M. R., Guy, C. D., Banerjee, R., Jaros, M. J., Owers, S., Baxter, B. A., et al. (2020) · Hepatology · doi:10.1002/hep.30590 · Cited by 262
“(4) Fibroblast growth factor 19 (FGF19), an endocrine gastrointestinal hormone, controls bile acid metabolism through actions on cholesterol 7alpha-hydroxylase (CYP7A1), the first and rate-limiting enzyme in the classic pathway of bile acid synthesis from cholesterol.(5) Multiple independent groups have reported reduc…”
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Crudele, L., Gadaleta, R. M., Cariello, M., & Moschetta, A. (2023) · eBioMedicine · doi:10.1016/j.ebiom.2023.104821 · Cited by 251
Self-citationMechanisms of muscle insulin resistance and the cross‐talk with liver and adipose tissue
Rosa, S. C. D. S., Nayak, N., Caymo, A. M., & Gordon, J. W. (2020) · Physiological Reports · doi:10.14814/phy2.14607 · Cited by 271
“and lipid metabolism, as well as the whole-body homeostasis (Degirolamo et al., 2016).”
BackgroundStructures of β-klotho reveal a ‘zip code’-like mechanism for endocrine FGF signalling
Lee, S., Choi, J., Mohanty, J., Sousa, L. P., Tome, F., Pardon, E., Steyaert, J., Lemmon, M. A., Lax, I., & Schlessinger, J. (2018) · Nature · doi:10.1038/nature25010 · Cited by 236
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Benoit, B., Meugnier, E., Castelli, M., Chanon, S., Vieille-Marchiset, A., Durand, C., Bendridi, N., Pesenti, S., Monternier, P.-A., Durieux, A.-C., et al. (2017) · Nature Medicine · doi:10.1038/nm.4363 · Cited by 225
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Saeed, A., Dullaart, R. P. F., Schreuder, T. C. M. A., Blokzijl, H., & Faber, K. N. (2017) · Nutrients · doi:10.3390/nu10010029 · Cited by 237
“FGF19 suppresses lipogenesis by blocking SREBP-1c signaling and simultaneously inducing fatty acid β-oxidation by blocking ACC2 (reviewed in [154]).”
BackgroundNew therapeutic concepts in bile acid transport and signaling for management of cholestasis
Trauner, M., Fuchs, C. D., Halilbasic, E., & Paumgartner, G. (2017) · Hepatology · doi:10.1002/hep.28991 · Cited by 227
“In addition to M70, several other FGF mimetics are available, which are, however, not yet explored for cholestasis.((55)) Administration of M70 in healthy human volunteers potently reduced serum levels of 7a-hydroxy-4cholesten-3-one (C4) as a surrogate marker for hepatic CYP7A1 activity((56)) (Table 1).”
Genetic insights into the mechanisms of Fgf signalingPreprint
Brewer, J. R., Mazot, P., & Soriano, P. M. (2016) · Genes & Development · doi:10.1101/gad.277137.115 · Cited by 230
“Several therapeutic strategies are currently being developed to modulate Fgfr signaling in various pathologies (Carter et al. 2015; Degirolamo et al. 2016).”
BackgroundTillman, E. J., & Rolph, T. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.601290 · Cited by 214
“Post prandial suppression of adipose tissue lipolysis by insulin is impaired(48),whileuptakebyadipose tissueofdietary fat as chylomicrons is also attenuated.”
BackgroundTherapeutics Targeting FGF Signaling Network in Human Diseases
Katoh, M. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.10.003 · Cited by 207
“FGF21 (LY2405319) [9_TD$DIFF] GF21 [14_TD$DIFF] receptor T2DM P1 (NCT01869959) [57]”
BackgroundInfluentialNovel therapeutic targets for cholestatic and fatty liver disease
Trauner, M., & Fuchs, C. D. (2022) · Gut · doi:10.1136/gutjnl-2021-324305 · Cited by 204
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“26 Although our results showed that concentrations of both phosphate and FGF23 increased after pemigatinib dosing, FGF23 concentration remained elevated during dosing holidays, whereas phosphate concentrations fell below baseline, suggesting that elevated FGF23 concentrations may be responsible for…”
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Jia, W. P., Li, Y., Cheung, K. C.-P., & Zheng, X. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2353-0 · Cited by 207
“Fibroblast growth factor 21 (FGF21) is a nutrient-sensing hormone that is produced in response to prolonged fasting in hepatocytes and adipose tissues, and was associated with BA levels and composition (Degirolamo et al., 2016).”
Hirschfield, G. M., Chazouillères, O., Drenth, J. P., Thorburn, D., Harrison, S. A., Landis, C. S., Mayo, M. J., Muir, A. J., Trotter, J. F., Leeming, D. J., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2018.10.035 · Cited by 187
“Ethnic origin, n (%) Hispanic/Latino 0 1 (5) 0”
BackgroundInfluentialAdipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions
de Oliveira dos Santos, A. R., de Oliveira Zanuso, B., Miola, V. F. B., Barbalho, S. M., Santos Bueno, P. C., Flato, U. A. P., Detregiachi, C. R. P., Buchaim, D. V., Buchaim, R. L., Tofano, R. J., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052639 · Cited by 189
Targeting FGFR inhibition in cholangiocarcinoma
Goyal, L., Kongpetch, S., Crolley, V. E., & Bridgewater, J. A. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102170 · Cited by 185
“important role in phosphate homeostasis [68,69] and FGFR1 is the predominant receptor for the hypophosphatemic action of FGF23 in vivo [70].”
BackgroundPathophysiological mechanisms underlying MAFLD
Kuchay, M. S., Choudhary, N. S., & Mishra, S. K. (2020) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2020.09.026 · Cited by 188
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Panzitt, K., & Wagner, M. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166133 · Cited by 170
Kumar, V., Xin, X., Ma, J., Tan, C., Osna, N. A., & Mahato, R. I. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113888 · Cited by 165
Zhou, M., Learned, R. M., Rossi, S. J., DePaoli, A. M., Tian, H., & Ling, L. (2017) · Hepatology Communications · doi:10.1002/hep4.1108 · Cited by 152
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BackgroundRoles of FGF Signals in Heart Development, Health, and Disease
Itoh, N., Ohta, H., Nakayama, Y., & Konishi, M. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00110 · Cited by 152
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Mengeste, A. M., Rustan, A. C., & Lund, J. (2021) · Obesity · doi:10.1002/oby.23227 · Cited by 141
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Ornitz, D. M., & Itoh, N. (2022) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1549 · Cited by 147
Harrison, S. A., Abdelmalek, M. F., Neff, G., Gunn, N., Guy, C. D., Alkhouri, N., Bashir, M. R., Freilich, B., Kohli, A., Khazanchi, A., et al. (2022) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(22)00017-6 · Cited by 148
Structural basis for FGF hormone signalling
Chen, L., Fu, L., Sun, J., Huang, Z., Fang, M., Zinkle, A., Liu, X., Lu, J., Pan, Z., Wang, Y., et al. (2023) · Nature · doi:10.1038/s41586-023-06155-9 · Cited by 147
“Lastly, we studied the possibility of FGFR heterodimerization by paracrine FGFs by focusing on: (1) FGFR1c–FGFR4 and FGFR1b–FGFR2b heterodimerizations by FGF1; (2) FGFR1b–FGFR2b heterodimerization by FGF10; and (3) FGFR2b–FGFR3b heterodimerization by FGF3.”
BackgroundLi, X. (2019) · Frontiers of Medicine · doi:10.1007/s11684-019-0711-y · Cited by 143
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Understanding bile acid signaling in diabetes: From pathophysiology to therapeutic targets
Ferrell, J. M., & Chiang, J. Y. L. (2019) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2019.0043 · Cited by 139
The role of adipokines in skeletal muscle inflammation and insulin sensitivity
Nicholson, T. A., Church, C., Baker, D. J., & Jones, S. W. (2018) · Journal of Inflammation · doi:10.1186/s12950-018-0185-8 · Cited by 133
“NCT01923389) [79–83], and antibodies targeting FGFR1c/ b-Klotho have been developed [84, 85].”
BackgroundEmerging hormonal-based combination pharmacotherapies for the treatment of metabolic diseases
Clemmensen, C., Finan, B., Müller, T. D., DiMarchi, R. D., Tschöp, M. H., & Hofmann, S. M. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0118-x · Cited by 129
Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis
Zhou, M., Yang, H., Learned, R. M., Tian, H., & Ling, L. (2017) · Nature Communications · doi:10.1038/ncomms15433 · Cited by 123
Targeting FGF21 in cardiovascular and metabolic diseases: from mechanism to medicine
Tan, H., Tong, Y. A., Chen, Z., Wu, W., Xu, S., & Weng, J. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.73936 · Cited by 119
“To overcome the weak binding affinity and instability of natural FGF21 [127], researchers analysed the structural and dynamic information of FGF21 and developed many FGF chimeras.”
BackgroundFibroblast Growth Factor 15/19: From Basic Functions to Therapeutic Perspectives
Somm, E., & Jornayvaz, F. R. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00134 · Cited by 124
From NAFLD to MAFLD: Definition, Pathophysiological Basis and Cardiovascular Implications
Boccatonda, A., Andreetto, L., D’Ardes, D., Cocco, G., Rossi, I., Vicari, S., Schiavone, C., Cipollone, F., & Guagnano, M. T. (2023) · Biomedicines · doi:10.3390/biomedicines11030883 · Cited by 116
“Another class of drugs under investigation are fibroblast growth factors (FGFs) 19 and 21 agonists that appear to improve the metabolic endocrine axis involving lipids, glucose and bile acids [92].”
BackgroundFGF1 — a new weapon to control type 2 diabetes mellitus
Gasser, E., Moutos, C. P., Downes, M., & Evans, R. M. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.78 · Cited by 107
Organ-organ communication: The liver's perspective
Wang, F., So, K., Xiao, J., & Wang, H. (2021) · Theranostics · doi:10.7150/thno.55795 · Cited by 107
“It has been recognized as a therapeutic target of obesity and diabetes [8].”
BackgroundBile acids and colon cancer: Is FXR the solution of the conundrum?
Gadaleta, R. M., García‐Irigoyen, O., & Moschetta, A. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.04.002 · Cited by 98
Lu, X., Chen, H., Patterson, A. V., Smaill, J. B., & Ding, K. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01531 · Cited by 99
Lang, L., & Teng, Y. (2019) · Cells · doi:10.3390/cells8010031 · Cited by 99
Restelli, L. M., Oettinghaus, B., Halliday, M., Ağca, C., Licci, M., Sironi, L., Savoia, C., Hench, J., Tolnay, M., Neutzner, A., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.023 · Cited by 98
Tiong, K. H., Tan, B. S., Choo, H. L., Chung, F. F., Hii, L., Tan, S. H., Khor, N. T., Wong, S. F., See, S.-J., Tan, Y.-F., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9328 · Cited by 96
“The significance of FGFs/ FGFRs signaling deregulation in breast cancers has been documented in several studies [13, 48, 49].”
BackgroundPathophysiological underpinnings of metabolic dysfunction-associated steatotic liver disease
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The Commensal Microbe V eillonella as a Marker for Response to an FGF19 Analog in NASH
Loomba, R., Ling, L., Dinh, D. M., DePaoli, A. M., Lieu, H. D., Harrison, S. A., & Sanyal, A. J. (2021) · Hepatology · doi:10.1002/hep.31523 · Cited by 88
“Fibroblast growth factor receptor 19 (FGF19) is a gut hormone that plays a central role in regulating bile acid metabolism.(17,18) Through the FGFR4-KLB receptor, FGF19 potently suppresses cholesterol 7alpha-hydroxylase (CYP7A1), which encodes the first and rate-liming enzyme in de novo synthesis of bile acids.”
BackgroundCellular Mechanisms of FGF-Stimulated Tissue Repair
Prudovsky, I. A. (2021) · Cells · doi:10.3390/cells10071830 · Cited by 94
“Another group (FGF 15/19, 21 and 23) consists of secreted hormone-like proteins regulating various aspects of organism metabolism [3].”
BackgroundThe FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives
Santolla, M. F., & Maggiolini, M. (2020) · Cancers · doi:10.3390/cancers12103029 · Cited by 89
Signaling pathways and intervention for therapy of type 2 diabetes mellitus
Cao, R. Y., Tian, H., Zhang, Y., Liu, G., Xu, H., Rao, G., Tian, Y., & Fu, X. (2023) · MedComm · doi:10.1002/mco2.283 · Cited by 98
Li, C., Chen, T., Liu, J., Wang, Y., Zhang, C., Guo, L., Shi, D., Zhang, T., Wang, X., & Li, J. (2023) · Advanced Science · doi:10.1002/advs.202302613 · Cited by 88
Effects of Periodic Fasting on Fatty Liver Index—A Prospective Observational Study
Drinda, S., Grundler, F., Neumann, T. E., Lehmann, T., Steckhan, N., Michalsen, A., & de Toledo, F. W. (2019) · Nutrients · doi:10.3390/nu11112601 · Cited by 87
“Although there is some evidence of impaired ketogenesis during the progression of liver disease to steatohepatitis, therapies that increase hepatic ketogenesis are expected nonetheless to ameliorate NAFLD [38,39].”
BackgroundJouy, S. H., Mohan, S., Scichilone, G., Mostafa, A., & Mahmoud, A. M. (2024) · Biomedicines · doi:10.3390/biomedicines12092129 · Cited by 96
Endocrine regulation of circadian physiology
Tsang, A. H. K., Astiz, M., Friedrichs, M., & Oster, H. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0051 · Cited by 86
“Its signals are mediated via its cognate receptors (FGF receptors FGFR1c, FGFR2c, or FGFR3c) in complex with β-Klotho abundantly expressed in metabolic tissues (Degirolamo et al. 2016).”
BackgroundLin, S., Mao, R., Qian, C., Bettenworth, D., Wang, J., Li, J., Bruining, D. H., Jairath, V., Feagan, B. G., Chen, M., et al. (2021) · Physiological Reviews · doi:10.1152/physrev.00005.2021 · Cited by 88
Circulating FGF21 Levels in Human Health and Metabolic Disease
Keuper, M., Häring, H., & Staiger, H. (2019) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-0879-2968 · Cited by 83
“, long-acting FGF21 analogues [3] or agonistic antibodies and small peptides targeting beta-klotho (KLΒ) [4], the crucial component of FGF21-receptor signaling complex.”
BackgroundSanyal, A. J., Ling, L., Beuers, U. H., DePaoli, A. M., Lieu, H. D., Harrison, S. A., & Hirschfield, G. M. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100255 · Cited by 80
Rinella, M. E., Trotter, J. F., Abdelmalek, M. F., Paredes, A. H., Connelly, M. A., Jaros, M. J., Ling, L., Rossi, S. J., DePaoli, A. M., & Harrison, S. A. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.11.032 · Cited by 83
Obesity: a perfect storm for carcinogenesis
Harris, B. H. L., Macaulay, V. M., Harris, D. A., Klenerman, P., Karpe, F., Lord, S., Harris, A. L., & Buffa, F. M. (2022) · Cancer and Metastasis Reviews · doi:10.1007/s10555-022-10046-2 · Cited by 84
“Conversely, FGF19 has been reported to be at lower levels in obese patient sera and this too may influence liver metabolism [295].”
BackgroundAngptl8 mediates food-driven resetting of hepatic circadian clock in mice
Chen, S., Feng, M., Zhang, S., Dong, Z., Wang, Y., Zhang, W., & Liu, C. (2019) · Nature Communications · doi:10.1038/s41467-019-11513-1 · Cited by 74
Multi-omics profiling: the way toward precision medicine in metabolic diseases
Hu, C., & Jia, W. (2021) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjab051 · Cited by 75
“Non-genetic markers for NALFD Another FGF family member, FGF19, binds to the FGFR4– b-klotho receptor complex, thus repressing the activation of cholesterol-7a-hydroxylase, sterol regulatory element-binding protein 1C, and cAMP-response element-binding protein, when induced by bile acids or FXR agonists to suppress th…”
BackgroundParacrine FGFs target skeletal muscle to exert potent anti-hyperglycemic effects
Lei, Y., Wang, L., Guo, K., Hou, Y., Li, N., Wang, S., Liu, X., Zhao, Q., Zhou, J., Zhao, L., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27584-y · Cited by 74
Fasting-induced hormonal regulation of lysosomal function
Chen, L., Wang, K., Long, A., Jia, L., Zhang, Y., Deng, H., Li, Y., Han, J., & Wang, Y. (2017) · Cell Research · doi:10.1038/cr.2017.45 · Cited by 71
Babaknejad, N., Nayeri, H., Hemmati, R., Bahrami, S., & Esmaillzadeh, A. (2018) · Hormone and Metabolic Research · doi:10.1055/a-0623-2909 · Cited by 70
“It is claimed that FGF15/19 activates ERK 1/2 signaling in adipocytes and increases glucose uptake [7, 8] (▶Fig.”
BackgroundCiaula, A. D., Bonfrate, L., Baj, J., Khalil, M., Garruti, G., Stellaard, F., Wang, H. H., Wang, D. Q. ‐., & Portincasa, P. (2022) · Nutrients · doi:10.3390/nu14234950 · Cited by 76
“FGFs belong to a family of at least 22 proteins with an effect on growth, development, and differentiation [90,94,95].”
BackgroundJin, L., Yang, R., Geng, L., & Xu, A. (2023) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-032322-093904 · Cited by 71
The role of FGF21 in the pathogenesis of cardiovascular disease
Zhang, Y., Liu, D., Long, X.-X., Fang, Q.-C., Jia, W.-P., & Li, H.-T. (2021) · Chinese Medical Journal · doi:10.1097/cm9.0000000000001890 · Cited by 68
“FGFs have therapeutic potential in a wide array of human diseases, including diabetes mellitus (DM),([16]) cancer,([17]) alopecia,([18]) and kidney disease.”
BackgroundVerzijl, C. R. C., van de Peppel, I. P., Struik, D., & Jonker, J. W. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1708898 · Cited by 67
“Compared to therapies based on other FGFs, such as FGF1 and FGF19, FGF21 has the advantage of being non-mitogenic [23,58].”
MethodTaming the Flames: Targeting White Adipose Tissue Browning in Hypermetabolic Conditions
Abdullahi, A., & Jeschke, M. G. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00163 · Cited by 68
Engineered biomaterial strategies for controlling growth factors in tissue engineering
Guan, N., Liu, Z., Zhao, Y., Li, Q., & Wang, Y. (2020) · Drug Delivery · doi:10.1080/10717544.2020.1831104 · Cited by 66
Phan, P., Saikia, B. B., Sonnaila, S., Agrawal, S., Alraawi, Z., Kumar, T. K. S., & Iyer, S. (2021) · Cells · doi:10.3390/cells10092418 · Cited by 70
“Therefore, the trend of endocrine FGFs research is focused on applying the fundamental knowledge to biomedical and clinical applications where many of them are at various phases of clinical trials (Table 1) [6,9,99,168].”
BackgroundThe role of fibroblast growth factor 21 in atherosclerosis
Kokkinos, J., Tang, S., Rye, K., & Ong, K. L. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.11.033 · Cited by 66
Guo, A., Li, K., & Xiao, Q. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.04.002 · Cited by 65
Translational Advances in Pediatric Nutrition and Gastroenterology: New Insights from Pig Models
Burrin, D. G., Sangild, P. T., Stoll, B., Thymann, T., Buddington, R. K., Marini, J. C., Olutoye, O. O., & Shulman, R. J. (2020) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-020518-115142 · Cited by 63
FGF21 attenuates pulmonary fibrogenesis through ameliorating oxidative stress in vivo and in vitro
Zhang, S., Yu, D., Wang, M., Huang, T., Wu, H., Zhang, Y., Zhang, T., Wang, W., Yin, J., Ren, G., et al. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.03.100 · Cited by 63
Struik, D., Dommerholt, M. B., & Jonker, J. W. (2019) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000599 · Cited by 61
Epigenetic Regulation of Hepatic Lipid Metabolism by DNA Methylation
Wang, S., Zha, L., Cui, X., Yeh, Y., Liu, R., Jing, J., Shi, H., Chen, W., Hanover, J. A., Yin, J., et al. (2023) · Advanced Science · doi:10.1002/advs.202206068 · Cited by 63
Kim, Y., Byun, S., Seok, S., Guo, G. L., Xu, H. E., KEMPER, B. W., & Kemper, J. K. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.11.061 · Cited by 61
Heianza, Y., Ma, W., Huang, T., Wang, T., Zheng, Y., Smith, S. R., Bray, G. A., Sacks, F. M., & Qi, L. (2016) · Diabetes Care · doi:10.2337/dc16-1111 · Cited by 60
“FGF21 has been attracting great interest as a whole-body metabolic regulator of energy balance and adipose metabolism (10,11) and also as a therapeutic potential for treatment of obesity (10).”
BackgroundTargeting the FGF19–FGFR4 pathway for cholestatic, metabolic, and cancerous diseases
Li, X., Lu, W., Kharitonenkov, A., & Luo, Y. (2024) · Journal of Internal Medicine · doi:10.1111/joim.13767 · Cited by 64
Metadata
- Authors
- Degirolamo, C., Sabbà, C., & Moschetta, A.
- Affiliations
- Istituto Tumori Bari (IT)
- University of Bari Aldo Moro (IT)
- Corresponding author
- Moschetta, Antonio
- Venue
- Nature Reviews Drug Discovery
- Published
- 2015-11-16
- Volume
- 15
- Issue
- 1
- Pages
- 51-69
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W2214871873
- Cited by
- 424
- References
- 240
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 36 · 2023: 42 · 2022: 55 · 2021: 48 · 2020: 54 · 2019: 43 · 2018: 41 · 2017: 36 · 2016: 18
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Keywords
- FGF19, FGF21, fibroblast growth factor 23, bile acid metabolism, glucose metabolism, lipid metabolism, vitamin D homeostasis, phosphate homeostasis, obesity, type 2 diabetes, cancer, kidney disease, cardiovascular disease
- MeSH terms
- Fibroblast Growth Factor-23, Animals, Chronic Disease, Fibroblast Growth Factors, Homeostasis, Humans, Models, Biological, Drugs, Investigational
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