Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice
Open accessAbstract
Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on regulating glucose and lipid homeostasis and insulin sensitivity. However, the mechanisms underlying the metabolic actions of FGF21 remain unknown. Here we show that the insulin-sensitizing adipokine adiponectin is a downstream effector of FGF21. Treatments with FGF21 enhanced both expression and secretion of adiponectin in adipocytes, thereby increasing serum levels of adiponectin in mice. Adiponectin knockout mice were refractory to several therapeutic benefits of FGF21, including alleviation of obesity-associated hyperglycemia, hypertriglyceridemia, insulin resistance, and hepatic steatosis. Furthermore, the effects of FGF21 on attenuation of obesity-induced impairment in insulin signaling in liver and skeletal muscle were abrogated in adiponectin knockout mice, whereas FGF21-mediated activation of ERK1/ERK2 in adipose tissues remained unaffected. Therefore, adiponectin couples FGF21 actions in local adipocytes to liver and skeletal muscle, thereby mediating the systemic effects of FGF21 on energy metabolism and insulin sensitivity.
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Hepatokines are a novel class of exercise-inducible soluble factors released by the liver during and after physical activity, including selenoprotein P, FGF21, HSP72, and hepassocin.
“Hepatokines represent a novel class of exercise-inducible soluble factors released by the liver during and after physical activity, including selenoprotein P (SeP) [93], FGF21 [118], heat shock protein 72 (HSP72) [119], and hepassocin (HPS) (Figure 3) [120].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [118]
Cites
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915 · see citing works
Weyer, C., Funahashi, T., Tanaka, S., Hotta, K., Matsuzawa, Y., Pratley, R. E., & Tataranni, P. A. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.5.7463 · Cited by 3,541 · see citing works
Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome
Kadowaki, T. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29126 · Cited by 2,824 · see citing works
The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
Berg, A. H., Combs, T. P., Du, X., Brownlee, M., & Scherer, P. E. (2001) · Nature Medicine · doi:10.1038/90992 · Cited by 2,526 · see citing works
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 · see citing works
Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504 · see citing works
Badman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495 · see citing works
Obesity-associated improvements in metabolic profile through expansion of adipose tissue
Kim, J.-Y., van de Wall, E., Laplante, M., Azzara, A., Trujillo, M. E., Hofmann, S. M., Schraw, T., Durand, J. L., Li, H., Li, G., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31021 · Cited by 1,310 · see citing works
Xu, A., Wang, Y., Keshaw, H., Xu, L. Y., Lam, K. S. L., & Cooper, G. J. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17797 · Cited by 1,298 · see citing works
Self-citationXu, A., Wang, Y., Keshaw, H., Xu, L. Y., Lam, K. S. L., & Cooper, G. J. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317797 · Cited by 1,298 · see citing works
Self-citationXu, J., Lloyd, D. J., Hale, C., Stanislaus, S., Chen, M., Sivits, G., Vonderfecht, S., Hecht, R., Li, Y.-S., Lindberg, R. A., et al. (2009) · Diabetes · doi:10.2337/db08-0392 · Cited by 1,151 · see citing works
Adiponectin and development of type 2 diabetes in the Pima Indian population
Lindsay, R. S., Funahashi, T., Hanson, R. L., Matsuzawa, Y., Tanaka, S., Tataranni, P. A., Knowler, W. C., & Krakoff, J. A. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09335-2 · Cited by 1,094 · see citing works
Fibroblast Growth Factor 21 Corrects Obesity in Mice
Coskun, T., Bina, H. A., Schneider, M. A., Dunbar, J. D., Hu, C. C., Chen, Y., Moller, D. E., & Kharitonenkov, A. (2008) · Endocrinology · doi:10.1210/en.2008-0816 · Cited by 1,031 · see citing works
Zhang, X., Yeung, D. C. Y., Karpisek, M., Stejskal, D., Zhou, Z.-G., Liu, F., Wong, R. L. C., Chow, W.-S., Tso, A. W. K., Lam, K. S. L., et al. (2008) · Diabetes · doi:10.2337/db07-1476 · Cited by 908 · see citing works
Self-citationObesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State
Fisher, F. M., Chui, P. C., Antonellis, P. J., Bina, H. A., Kharitonenkov, A., Flier, J. S., & Maratos-Flier, E. (2010) · Diabetes · doi:10.2337/db10-0193 · Cited by 830 · see citing works
Iwaki, M., Matsuda, M., Maeda, N., Funahashi, T., Matsuzawa, Y., Makishima, M., & Shimomura, I. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1655 · Cited by 740 · see citing works
The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21
Kharitonenkov, A., Wroblewski, V. J., Koester, A., Chen, Y.-F., Clutinger, C. K., Tigno, X. T., Hansen, B. C., Shanafelt, A. B., & Etgen, G. J. (2007) · Endocrinology · doi:10.1210/en.2006-1168 · Cited by 738 · see citing works
Potthoff, M. J., Inagaki, T., Satapati, S., Ding, X., He, T., Goetz, R., Mohammadi, M., Finck, B. N., Mangelsdorf, D. J., Kliewer, S. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904187106 · Cited by 704 · see citing works
Nawrocki, A. R., Rajala, M. W., Tomás, E., Pajvani, U. B., Saha, A. K., Trumbauer, M. E., Pang, Z., Chen, A. S., Ruderman, N. B., Chen, H., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505311200 · Cited by 640 · see citing works
Thermogenic Activation Induces FGF21 Expression and Release in Brown Adipose Tissue
Hondares, E., Iglesias, R., Giralt, A., Gonzalez, F. J., Giralt, M., Mampel, T., & Villarroya, F. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.215889 · Cited by 623 · see citing works
Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK–SIRT1–PGC-1α pathway
Chau, M. D. L., Gao, J., Yang, Q., Wu, Z., & Gromada, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006962107 · Cited by 548 · see citing works
Dutchak, P. A., Katafuchi, T., Bookout, A. L., Choi, J. H., Yu, R. T., Mangelsdorf, D. J., & Kliewer, S. A. (2012) · Cell · doi:10.1016/j.cell.2011.11.062 · Cited by 537 · see citing works
Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes
Faßhauer, M., Kralisch, S., Klier, M., Lössner, U., Blüher, M., Klein, J. C., & Paschke, R. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00090-1 · Cited by 534 · see citing works
Endocrine fibroblast growth factors 15/19 and 21: from feast to famine
Potthoff, M. J., Kliewer, S. A., & Mangelsdorf, D. J. (2012) · Genes & Development · doi:10.1101/gad.184788.111 · Cited by 442 · see citing works
Xu, A., Chan, K. W., Hoo, R. L. C., Wang, Y., Tan, K. C. B., Zhang, J., Chen, B., Lam, M. C., Tse, C. A., Cooper, G. J. S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414231200 · Cited by 418 · see citing works
Self-citationPost-translational modifications of adiponectin: mechanisms and functional implications
Wang, Y., Lam, K. S. L., Yau, M.-H., & Xu, A. (2008) · Biochemical Journal · doi:10.1042/bj20071492 · Cited by 405 · see citing works
Self-citationβKlotho Is Required for Fibroblast Growth Factor 21 Effects on Growth and Metabolism
Ding, X., Boney-Montoya, J., Owen, B. M., Bookout, A. L., Coate, K. C., Mangelsdorf, D. J., & Kliewer, S. A. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.002 · Cited by 403 · see citing works
Hotta, Y., Nakamura, H., Konishi, M., Murata, Y., Takagi, H., Matsumura, S., Inoue, K., Fushiki, T., & Itoh, N. (2009) · Endocrinology · doi:10.1210/en.2009-0119 · Cited by 352 · see citing works
Suzuki, M., Uehara, Y., Motomura-Matsuzaka, K., Oki, J., Koyama, Y., Kimura, M., Asada, M., Komi-Kuramochi, A., Oka, S., & Toru, T. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0313 · Cited by 345 · see citing works
FGF‐21/FGF‐21 receptor interaction and activation is determined by βKlotho
Kharitonenkov, A., Dunbar, J. D., Bina, H. A., Bright, S. W., Moyers, J. S., Zhang, C., Ding, L., Micanovic, R., Mehrbod, S. F., Knierman, M. D., et al. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21357 · Cited by 329 · see citing works
Kubota, N., Terauchi, Y., Kubota, T., Kumagai, H., Itoh, S., Satoh, H., Yano, W., Ogata, H., Tokuyama, K., Takamoto, I., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m505649200 · Cited by 327 · see citing works
Wang, Z. V., Schraw, T., Kim, J., Khan, T., Rajala, M. W., Follenzi, A., & Scherer, P. E. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00931-06 · Cited by 305 · see citing works
Berglund, E. D., Li, C. Y., Bina, H. A., Lynes, S. E., Michael, M. D., Shanafelt, A. B., Kharitonenkov, A., & Wasserman, D. H. (2009) · Endocrinology · doi:10.1210/en.2009-0221 · Cited by 297 · see citing works
Increased β-Oxidation but No Insulin Resistance or Glucose Intolerance in Mice Lacking Adiponectin
Ma, K., Cabrero, À., Saha, P., Kojima, H., Li, L., Chang, B. H.-J., Paul, A., & Chan, L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200362200 · Cited by 284 · see citing works
The breadth of FGF21's metabolic actions are governed by FGFR1 in adipose tissue
Adams, A. C., Yang, C., Coskun, T., Cheng, C. C., Gimeno, R. E., Luo, Y., & Kharitonenkov, A. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2012.08.007 · Cited by 266 · see citing works
Wang, Y., Lam, K. S. L., Chan, L., Chan, K. W., Lam, J. B. B., Lam, M. C., Hoo, R. L. C., Mak, W. W. N., Cooper, G. J. S., & Xu, A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513907200 · Cited by 254 · see citing works
Self-citationTranscriptional and post-translational regulation of adiponectin
Liu, M., & Liu, F. (2009) · Biochemical Journal · doi:10.1042/bj20091045 · Cited by 235 · see citing works
Integrated Regulation of Hepatic Metabolism by Fibroblast Growth Factor 21 (FGF21) in Vivo
Fisher, F. M., Estall, J. L., Adams, A. C., Antonellis, P. J., Bina, H. A., Flier, J. S., Kharitonenkov, A., Spiegelman, B. M., & Maratos–Flier, E. (2011) · Endocrinology · doi:10.1210/en.2011-0281 · Cited by 229 · see citing works
A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization
Liu, M., Zhou, L., Xu, A., Lam, K. S. L., Wetzel, M. D., Xiang, R., Zhang, J., Xin, X., Dong, L., & Liu, F. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806341105 · Cited by 207 · see citing works
Self-citationDíaz-Delfín, J., Hondares, E., Iglesias, R., Giralt, M., Caelles, C., & Villarroya, F. (2012) · Endocrinology · doi:10.1210/en.2012-1193 · Cited by 195 · see citing works
Li, H., Gao, Z., Zhang, J., Ye, X., Xu, A., Ye, J., & Jia, W. (2012) · Diabetes · doi:10.2337/db11-0846 · Cited by 193 · see citing works
Self-citationGe, X., Chen, C., Hui, X. H., Wang, Y., Lam, K. S. L., & Xu, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.248591 · Cited by 181 · see citing works
Self-citationHigh Plasma Level of Fibroblast Growth Factor 21 Is an Independent Predictor of Type 2 Diabetes
Chen, C., Cheung, B. M. Y., Tso, A. W. K., Wang, Y., Law, L. S., Ong, K. L., Wat, N. M. S., Xu, A., & Lam, K. S. L. (2011) · Diabetes Care · doi:10.2337/dc11-0294 · Cited by 181 · see citing works
Self-citationDifferential Specificity of Endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in Complex with KLB
Yang, C., Jin, C., Li, X., Wang, F., McKeehan, W. L., & Luo, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033870 · Cited by 173 · see citing works
Self-citationYu, H., Xia, F., Lam, K. S., Wang, Y., Bao, Y., Zhang, J., Gu, Y., Zhou, P., Lu, J., Jia, W., et al. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2010.155184 · Cited by 170 · see citing works
Self-citationChen, W., Hoo, R. L. C., Konishi, M., Itoh, N., Lee, P.-C., Ye, H., Lam, K. S. L., & Xu, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.285965 · Cited by 141 · see citing works
Self-citationFGF21 Promotes Metabolic Homeostasis via White Adipose and Leptin in Mice
Véniant, M. M., Hale, C., Helmering, J., Chen, M. M., Stanislaus, S., Busby, J., Vonderfecht, S., Xu, J., & Lloyd, D. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040164 · Cited by 141 · see citing works
Chang, J., Li, Y., Huang, Y., Lam, K. S. L., Hoo, R. L. C., Wong, W. T., Cheng, K. K. Y., Wang, Y., Vanhoutte, P. M., & Xu, A. (2010) · Diabetes · doi:10.2337/db10-0582 · Cited by 113 · see citing works
Self-citationXu, A., Wang, H., Hoo, R. L. C., Sweeney, G., Vanhoutte, P. M., Wang, Y., Wu, D., Chu, W., Qin, G., & Lam, K. S. L. (2008) · Endocrinology · doi:10.1210/en.2008-0999 · Cited by 107 · see citing works
Self-citationZhou, M., Xu, A., Tam, P. K. H., Lam, K. S. L., Chan, L., Hoo, R. L. C., Liu, J., Chow, H., & Wang, Y. (2008) · Hepatology · doi:10.1002/hep.22444 · Cited by 82 · see citing works
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Ornitz, D. M., & Itoh, N. (2015) · WIREs Developmental Biology · doi:10.1002/wdev.176 · Cited by 2,050 · see citing works
Self-citationUnderstanding the Physiology of FGF21
Fisher, F. M., & Maratos-Flier, E. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105339 · Cited by 912 · see citing works
Exerkines in health, resilience and disease
Chow, L. S., Gerszten, R. E., Taylor, J. M., Pedersen, B. K., van Praag, H., Trappe, S., Febbraio, M. A., Galis, Z. S., Gao, Y., Haus, J. M., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00641-2 · Cited by 927 · see citing works
FGF/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 · see citing works
The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes
Gaich, G., Chien, J. Y., Fu, H., Glass, L. C., Deeg, M. A., Holland, W. L., Kharitonenkov, A., Bumol, T., Schilske, H. K., & Moller, D. E. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.005 · Cited by 885 · see citing works
Targeting adipose tissue in the treatment of obesity-associated diabetes
Kusminski, C. M., Bickel, P. E., & Scherer, P. E. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.75 · Cited by 678 · see citing works
The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic
Geng, L., Lam, K. S. L., & Xu, A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0386-0 · Cited by 607 · see citing works
Self-citationCirculating FGF21 Is Liver Derived and Enhances Glucose Uptake During Refeeding and Overfeeding
Markan, K. R., Naber, M. C., Ameka, M. K., Anderegg, M. D., Mangelsdorf, D. J., Kliewer, S. A., Mohammadi, M., & Potthoff, M. J. (2014) · Diabetes · doi:10.2337/db14-0595 · Cited by 590 · see citing works
New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond
Beuers, U., Trauner, M., Jansen, P., & Poupon, R. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.023 · Cited by 537 · see citing works
FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss
Owen, B. M., Ding, X., Morgan, D. A., Coate, K. C., Bookout, A. L., Rahmouni, K., Kliewer, S. A., & Mangelsdorf, D. J. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.07.012 · Cited by 523 · see citing works
Decreased consumption of branched-chain amino acids improves metabolic health
Fontana, L., Cummings, N. E., Arriola Apelo, S. I., Neuman, J. C., Kasza, I., Schmidt, B. A., Cava, E., Spelta, F., Tosti, V., Syed, F. A., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.092 · Cited by 466 · see citing works
Talukdar, S., Zhou, Y., Li, D., Rossulek, M., Dong, J., Somayaji, V., Weng, Y., Clark, R., Lanba, A., Owen, B. M., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.02.001 · Cited by 496 · see citing works
Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23
Degirolamo, C., Sabbà, C., & Moschetta, A. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.9 · Cited by 424 · see citing works
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BonDurant, L. D., Ameka, M., Naber, M. C., Markan, K. R., Idiga, S. O., Acevedo, M. R., Walsh, S. A., Ornitz, D. M., & Potthoff, M. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.005 · Cited by 330 · see citing works
Flippo, K. H., & Potthoff, M. J. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00354-2 · Cited by 311 · see citing works
Liang, Q., Zhong, L., Zhang, J., Wang, Y., Bornstein, S. R., Triggle, C. R., Ding, H., Lam, K. S. L., & Xu, A. (2014) · Diabetes · doi:10.2337/db14-0541 · Cited by 299 · see citing works
Myokines and Adipokines: Involvement in the Crosstalk between Skeletal Muscle and Adipose Tissue
Li, F., Li, Y., Duan, Y., Hu, C.-A. A., Tang, Y., & Yin, Y. (2017) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.10.003 · Cited by 288 · see citing works
Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21
Owen, B. M., Mangelsdorf, D. J., & Kliewer, S. A. (2015) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2014.10.002 · Cited by 286 · see citing works
Bo, T., Gao, L., Yao, Z., Shao, S., Wang, X., Proud, C. G., & Zhao, J. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.04.006 · Cited by 293 · see citing works
Cytokines and abnormal glucose and lipid metabolism
Shi, J., Fan, J., Su, Q., & Yang, Z. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00703 · Cited by 282 · see citing works
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278 · see citing works
Fibroblast 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 · see citing works
Lan, T., Morgan, D. A., Rahmouni, K., Sonoda, J., Fu, X., Burgess, S. C., Holland, W. L., Kliewer, S. A., & Mangelsdorf, D. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.005 · Cited by 261 · see citing works
Fisher, F. M., Chui, P. C., Nasser, I. A., Popov, Y., Cunniff, J. C., Lundasen, T., Kharitonenkov, A., Schuppan, D., Flier, J. S., & Maratos-Flier, E. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.07.044 · Cited by 263 · see citing works
Schlein, C., Talukdar, S., Heine, M., Fischer, A. W., Krott, L. M., Nilsson, S. K., Brenner, M. B., Heeren, J., & Scheja, L. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.01.006 · Cited by 252 · see citing works
Keipert, S., Ost, M., Johann, K., Imber, F., Jastroch, M., van Schothorst, E. M., Keijer, J., & Klaus, S. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00330.2013 · Cited by 221 · see citing works
Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis
BonDurant, L. D., & Potthoff, M. J. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064800 · Cited by 222 · see citing works
Metabolic adaptation in obesity and type ii diabetes: myokines, adipokines and hepatokines
Oh, K.-J., Lee, D., Kim, W., Han, B., Lee, S., & Bae, K.-H. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms18010008 · Cited by 210 · see citing works
Action and therapeutic potential of oxyntomodulin
Pocai, A. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2013.12.001 · Cited by 191 · see citing works
LY2405319, an engineered FGF21 variant, improves the metabolic status of diabetic monkeys
Adams, A. C., Halstead, C. A., Hansen, B. C., Irizarry, A. R., Martin, J. A., Myers, S. R., Reynolds, V. L., Smith, H. W., Wroblewski, V. J., & Kharitonenkov, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065763 · Cited by 169 · see citing works
FGF21-based pharmacotherapy – potential utility for metabolic disorders
Gimeno, R. E., & Moller, D. E. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2014.03.001 · Cited by 163 · see citing works
Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21
Dunshee, D. R., Bainbridge, T. W., Kljavin, N. M., Zavala-Solorio, J., Schroeder, A. C., Chan, R., Corpuz, R., Wong, M., Zhou, W., Deshmukh, G., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.710582 · Cited by 158 · see citing works
Discrete Aspects of FGF21 In Vivo Pharmacology Do Not Require UCP1
Samms, R. J., Smith, D. P., Cheng, C. C., Antonellis, P. P., Perfield, J. W., Kharitonenkov, A., Gimeno, R. E., & Adams, A. C. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.046 · Cited by 154 · see citing works
Fibroblast growth factor 21 and browning of white adipose tissue
Cuevas-Ramos, D., Mehta, R., & Aguilar-Salinas, C. A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00037 · Cited by 149 · see citing works
Huang, Z., Zhong, L., Lee, J. T. H., Zhang, J., Wu, D., Geng, L., Wang, Y., Wong, C.-M., & Xu, A. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.003 · Cited by 147 · see citing works
Self-citationKim, K. H., & Lee, M.-S. (2014) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2014.38.4.245 · Cited by 146 · see citing works
Wanders, D., Forney, L. A., Stone, K. P., Burk, D. H., Pierse, A., & Gettys, T. W. (2017) · Diabetes · doi:10.2337/db16-1212 · Cited by 137 · see citing works
Kaufman, A., Abuqayyas, L., Denney, W. S., Tillman, E. J., & Rolph, T. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100057 · Cited by 131 · see citing works
Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates
Lundsgaard, A.-M., Fritzen, A. M., Sjøberg, K. A., Myrmel, L. S., Madsen, L., Wojtaszewski, J. F. P., Richter, E. A., & Kiens, B. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2016.11.001 · Cited by 126 · see citing works
Kim, S. H., Kim, K. H., Kim, H.-K., Kim, M.-J., Back, S. H., Konishi, M., Itoh, N., & Lee, M.-S. (2015) · Diabetologia · doi:10.1007/s00125-014-3475-6 · Cited by 124 · see citing works
Self-citationRegulation of longevity by FGF21: interaction between energy metabolism and stress responses
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.05.004 · Cited by 121 · see citing works
Harrison, S. A., Ruane, P. J., Freilich, B., Neff, G., Patil, R., Behling, C., Hu, C., Shringarpure, R., de Temple, B., Fong, E., et al. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2022.100563 · Cited by 110 · see citing works
Kolumam, G., Chen, M. Z., Tong, R., Zavala-Solorio, J., Kates, L., van Bruggen, N., Ross, J., Wyatt, S. K., Gandham, V. D., Carano, R. A. D., et al. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.05.028 · Cited by 108 · see citing works
Metabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis
Markan, K. R., & Potthoff, M. J. (2016) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2015.09.021 · Cited by 103 · see citing works
Adiponectin resistance in skeletal muscle: Pathophysiological implications in chronic heart failure
Sente, T., Van Berendoncks, A. M., Hoymans, V. Y., & Vrints, C. J. (2016) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12086 · Cited by 95 · see citing works
Baruch, A., Wong, C., Chinn, L. W., Vaze, A., Sonoda, J., Gelzleichter, T., Chen, S., Lewin-Koh, N., Morrow, L., Dheerendra, S., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2012073117 · Cited by 95 · see citing works
Muscle mitochondrial stress adaptation operates independently of endogenous FGF21 action
Ost, M., Coleman, V., Voigt, A., van Schothorst, E. M., Keipert, S., van der Stelt, I., Ringel, S., Graja, A., Ambrosi, T., Kipp, A. P., et al. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2015.11.002 · Cited by 75 · see citing works
Wang, K., Li, F., Wang, C., Deng, Y., Cao, Z., Cui, Y., Xu, K., Ln, P., & Sun, Y. (2019) · Medical Science Monitor · doi:10.12659/msm.915331 · Cited by 71 · see citing works
Adiponectin as a tissue regenerating hormone: More than a metabolic function
Fiaschi, T., Magherini, F., Gamberi, T., Modesti, P. A., & Modesti, A. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1537-4 · Cited by 66 · see citing works
Adipose–Muscle Crosstalk in Age-Related Metabolic Disorders: The Emerging Roles of Adipo-Myokines
Fang, P., She, Y., Yu, M., Min, W., Shang, W., & Zhang, Z. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101829 · Cited by 62 · see citing works
Myokines as possible therapeutic targets in cancer cachexia
Manole, E., Ceafalan, L. C., Popescu, B. O., Dumitru, C., & Bastian, A. E. (2018) · Journal of Immunology Research · doi:10.1155/2018/8260742 · Cited by 60 · see citing works
Muise, E. S., Souza, S., Chi, A., Tan, Y., Zhao, X., Liu, F., Dallas-yang, Q., Wu, M., Sarr, T., Zhu, L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073011 · Cited by 57 · see citing works
Myokines: Metabolic regulation in obesity and type 2 diabetes
Chen, Z.-T., Weng, Z.-X., Lin, J. D., & Meng, Z.-X. (2024) · Life Metabolism · doi:10.1093/lifemeta/loae006 · Cited by 58 · see citing works
GLP‐1 receptor agonists: effects on the progression of non‐alcoholic fatty liver disease
Liu, J., Wang, G., Jia, Y., & Xu, Y. (2015) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2580 · Cited by 48 · see citing works
(2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.012 · Cited by 46 · see citing works
A feed-forward regulatory loop in adipose tissue promotes signaling by the hepatokine FGF21
Han, M. S., Perry, R. J., Camporez, J.-P., Scherer, P. E., Shulman, G. I., Gao, G., & Davis, R. J. (2021) · Genes & Development · doi:10.1101/gad.344556.120 · Cited by 43 · see citing works
Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis
Wang, J., Jia, D., Zhang, Z., & Wang, D. (2025) · Metabolites · doi:10.3390/metabo15010059 · Cited by 23 · see citing works
Guru, B., Tamrakar, A. K., Manjula, S. N., & Prashantha Kumar, B. R. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175322 · Cited by 18 · see citing works
- Authors
- Lin, Z., Tian, H., Lam, K. S. L., Lin, S., Hoo, R. C. L., Konishi, M., Itoh, N., Wang, Y., Bornstein, S. R., Xu, A., & Li, X.
- Affiliations
- Wenzhou Medical University (CN)
- University of Hong Kong (HK)
- Kyoto University (JP)
- Corresponding author
- Xu, Aimin
- Li, Xiaokun
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 17
- Issue
- 5
- Pages
- 779-789
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2100232436
- Cited by
- 691
- References
- 50
- Citations by year
- 2026: 28 · 2025: 50 · 2024: 56 · 2023: 53 · 2022: 69 · 2021: 55 · 2020: 43 · 2019: 47 · 2018: 48 · 2017: 54 · 2016: 60 · 2015: 56 · 2014: 49 · 2013: 21
- FWCI
- 27.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- FGF21, adiponectin, insulin sensitivity, glucose homeostasis, insulin resistance, obesity, hypertriglyceridemia, hepatic steatosis, adipocytes, ERK1/ERK2 signaling, energy metabolism, metabolic hormones, adipokines, skeletal muscle insulin signaling
- MeSH terms
- Animals, Energy Metabolism, Fatty Acids, Fatty Liver, Fibroblast Growth Factors, Glucose, Homeostasis, Hyperglycemia, Insulin Resistance, Liver, Male, Mice, Inbred C57BL, Obesity, Oxidation-Reduction, Hypertriglyceridemia, Adipocytes, Muscle, Skeletal, MAP Kinase Signaling System, Mice, Adiponectin
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