The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin-resistant mouse models—association with liver and adipose tissue effects
Abstract
Recombinant fibroblast growth factor (FGF)21 has antihyperglycemic, antihyperlipidemic, and antiobesity effects in diabetic rodent and monkey models. Previous studies were confined to measuring steady-state effects of FGF21 following subchronic or chronic administration. The present study focuses on the kinetics of biological actions of FGF21 following a single injection and on the associated physiological and cellular mechanisms underlying FGF21 actions. We show that FGF21 resulted in rapid decline of blood glucose levels and immediate improvement of glucose tolerance and insulin sensitivity in two animal models of insulin resistance ( ob/ob and DIO mice). In ob/ob mice, FGF21 led to a 40–60% decrease in blood glucose, insulin, and amylin levels within 1 h after injection, and the maximal effects were sustained for more than 6 h despite the 1- to 2-h half-life of FGF21. In DIO mice, FGF21 reduced fasting blood glucose and insulin levels and improved glucose tolerance and insulin sensitivity within 3 h of treatment. The acute improvement of glucose metabolism was associated with a 30% reduction of hepatic glucose production and an increase in peripheral glucose turnover. FGF21 appeared to have no direct effect on ex vivo pancreatic islet insulin or glucagon secretion. However, it rapidly induced typical FGF signaling in liver and adipose tissues and in several hepatoma-derived cell lines and differentiated adipocytes. FGF21 was able to inhibit glucose release from H4IIE hepatoma cells and stimulate glucose uptake in 3T3-L1 adipocytes. We conclude that the acute glucose-lowering and insulin-sensitizing effects of FGF21 are potentially associated with its metabolic actions in liver and adipose tissues.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Once secreted, FGF21 has a short half-life of approximately 0.5–1.5 hours (refs. 40,41).”
From Metabolic messengers: FGF21 (2021) · cites this paper as [41]
In the citing paper
“This decrease in plasma glucose levels occurs primarily through increased peripheral glucose disposal41,56,65, although decreases in hepatic glucose production have also been observed66.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [41]
In the citing paper
“A single injection of FGF21 can decrease plasma glucose levels by more than 50% in animal models with genetically induced and diet-induced obesity41,65.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [41]
In the citing paper
“KLB expression is primarily restricted to specific metabolic tissues (for example, the liver, pancreas and adipose tissue)5, and lower expression is observed in the brain22,48–50. Despite some reports to the contrary51,52, KLB is not expressed in muscle5,41.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [41]
In the citing paper
“FGF21 signalling to adipose tissues promotes the disposal of excess carbohydrates41,65.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [41]
In the citing paper
“Pharmacological administration of FGF21 decreases plasma glucose and lipid levels, improves insulin and leptin sensitivity, decreases hepatic steatosis, increases energy expenditure [[131], [132], [133], [134], [135], [136]], and decreases sugar and alcohol intake in mice [[137], [138], [139], [140], [141], [142]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [132]
In the citing paper
“Pharmacological administration of FGF21 decreases plasma glucose and lipid levels, improves insulin and leptin sensitivity, decreases hepatic steatosis, increases energy expenditure [[131], [132], [133], [134], [135], [136]], and decreases sugar and alcohol intake in mice [[137], [138], [139], [140], [141], [142]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [132]
In the citing paper
“Pharmacological administration of FGF21 decreases plasma glucose and lipid levels, improves insulin and leptin sensitivity, decreases hepatic steatosis, increases energy expenditure [[131], [132], [133], [134], [135], [136]], and decreases sugar and alcohol intake in mice [[137], [138], [139], [140], [141], [142]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [132]
In the citing paper
“Pharmacological administration of FGF21 decreases plasma glucose and lipid levels, improves insulin and leptin sensitivity, decreases hepatic steatosis, increases energy expenditure [[131], [132], [133], [134], [135], [136]], and decreases sugar and alcohol intake in mice [[137], [138], [139], [140], [141], [142]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [132]
In the citing paper
“The acute pharmacological administration of FGF21 increases insulin sensitivity and lowers plasma glucose levels, primarily by stimulating peripheral glucose disposal, while also slightly reducing hepatic glucose production (27, 142).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [142]
In the citing paper
“A single injection of FGF21 to diabetic and obese animal models is sufficient to decrease plasma glucose levels by more than 50% (142).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [142]
In the citing paper
“The half-life of FGF21 is approximately 0.4–2 hours, depending on the species and method of delivery (51, 65, 142).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [142]
Citations
Cites
Wild, S., Roglic, G., Green, A., Sicree, R., & King, H. (2004) · Diabetes Care · doi:10.2337/diacare.27.5.1047 · Cited by 15,297
Method for the Isolation of Intact Islets of Langerhans from the Rat Pancreas
Lacy, P. E., & Kostianovsky, M. (1967) · Diabetes · doi:10.2337/diab.16.1.35 · Cited by 2,741
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
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
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
Self-citationAdvances in Male Contraception
Page, S. T., Amory, J. K., & Bremner, W. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0041 · Cited by 1,138
Evolution of the Fgf and Fgfr gene families.
Itoh, N., & Ornitz, D. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.08.007 · Cited by 1,123
Identification of a novel FGF, FGF-21, preferentially expressed in the liver
Nishimura, T., Nakatake, Y., Konishi, M., & Itoh, N. (2000) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(00)00067-1 · Cited by 847
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
βKlotho is required for metabolic activity of fibroblast growth factor 21
Ogawa, Y., Kurosu, H., Yamamoto, M., Nandi, A., Rosenblatt, K. P., Goetz, R., Eliseenkova, A. V., Mohammadi, M., & Kuro-o, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701600104 · Cited by 617
Research works printed but not linked: 2
- Dostalova I, 2009, Physiol Res/Academia Scientiarum Bohemoslovaca, 58, 1
- Kharitonenkov A, 2009, Curr Opin Investig Drugs, 10, 359
Cited by
Sorted by citations
Bispecific antibodies: a mechanistic review of the pipeline
Labrijn, A. F., Janmaat, M. L., Reichert, J. M., & Parren, P. W. H. I. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0028-1 · Cited by 1,303
Understanding 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
Obesity 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
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
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
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
Increased Fibroblast Growth Factor 21 in Obesity and Nonalcoholic Fatty Liver Disease
Dushay, J., Chui, P. C., Gopalakrishnan, G. S., Varela–Rey, M., Crawley, M., Fisher, F. M., Badman, M. K., Martinez–Chantar, M. L., & Maratos–Flier, E. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.04.054 · Cited by 607
Circulating 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
Sanyal, A., Charles, E. D., Neuschwander-Tetri, B. A., Loomba, R., Harrison, S. A., Abdelmalek, M. F., Lawitz, E. J., Halegoua-DeMarzio, D., Kundu, S., Noviello, S., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31785-9 · Cited by 550
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
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
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
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
Fibroblast growth factor 21 protects against cardiac hypertrophy in mice
Planavila, A., Redondo‐Angulo, I., Hondares, E., Vinciguerra, M., Munts, C., Iglesias, R., Gabrielli, L., Sitges, M., Giralt, M., van Bilsen, M., et al. (2013) · Nature Communications · doi:10.1038/ncomms3019 · Cited by 371
Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication
Funcke, J., & Scherer, P. E. (2019) · Journal of Lipid Research · doi:10.1194/jlr.r094060 · Cited by 357
FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms
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
FGF21 gene therapy as treatment for obesity and insulin resistance
Jiménez, V., Jambrina, C., Casana, E., Sacristan, V., MUÑOZ, S. A., Darriba, S., Rodó, J., Mallol, C., García, M., León, X., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708791 · Cited by 319
FGF21 as Modulator of Metabolism in Health and Disease
Tezze, C., Romanello, V., & Sandri, M. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00419 · Cited by 319
Flippo, K. H., & Potthoff, M. J. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00354-2 · Cited by 311
Zaykov, A. N., Mayer, J. P., & DiMarchi, R. D. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.36 · Cited by 294
Noble, E. E., Billington, C. J., Kotz, C. M., & Wang, C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00776.2010 · Cited by 284
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
Charles, E. D., Neuschwander‐Tetri, B. A., Pablo Frias, J., Kundu, S., Luo, Y., Tirucherai, G. S., & Christian, R. (2019) · Obesity · doi:10.1002/oby.22344 · Cited by 257
“Endogenous FGF21 has a short half-life; analogs with extended half-lives improve insulin sensitivity and lipid profiles in preclinical and clinical studies (5-7).”
ResultInfluentialSchlein, 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
Hepatokines and metabolism: Deciphering communication from the liver
Jensen-Cody, S. O., & Potthoff, M. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101138 · Cited by 252
Brown Adipose Tissue Responds to Cold and Adrenergic Stimulation by Induction of FGF21
Chartoumpekis, D. V., Habeos, I. G., Ziros, P. G., Psyrogiannis, A. I., Kyriazopoulou, V. E., & Papavassiliou, A. G. (2011) · Molecular Medicine · doi:10.2119/molmed.2011.00075 · Cited by 252
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 231
Brown adipose tissue and thermogenesis
Fenzl, A., & Kiefer, F. W. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2014-0022 · Cited by 239
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
Glucagon Receptor Signaling and Lipid Metabolism
Galsgaard, K. D., Pedersen, J., Knop, F. K., Holst, J. J., & Wewer Albrechtsen, N. J. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00413 · Cited by 218
FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans
Søberg, S., Sandholt, C. H., Jespersen, N. Z., Toft, U., Madsen, A. L., von Holstein-Rathlou, S., Grevengoed, T. J., Christensen, K. B., Bredie, W. L. P., Potthoff, M. J., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.009 · Cited by 216
FGF21 and the late adaptive response to starvation in humans
Fazeli, P. K., Lun, M., Kim, S. M., Bredella, M. A., Wright, S., Zhang, Y., Lee, H., Catana, C., Klibanski, A., Patwari, P., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci83349 · Cited by 214
Gehrke, N., & Schattenberg, J. M. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.02.020 · Cited by 216
Lees, E. K., Król, E., Grant, L., Shearer, K., Wyse, C. A., Moncur, E. M., Bykowska, A. S., Mody, N., Gettys, T. W., & Delibegović, M. (2014) · Aging Cell · doi:10.1111/acel.12238 · Cited by 203
Mechanisms of Increased In Vivo Insulin Sensitivity by Dietary Methionine Restriction in Mice
Stone, K. P., Wanders, D., Orgeron, M., Cortez, C. C., & Gettys, T. W. (2014) · Diabetes · doi:10.2337/db14-0464 · Cited by 201
Vernia, S., Cavanagh, J., García-Haro, L., Sabio, G., Barrett, T., Jung, D. Y., Kim, J. K., Xu, J. L., Shulha, H. P., Garber, M. G., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.06.010 · Cited by 200
Self-citationInventing new medicines: The FGF21 story
Kharitonenkov, A., & Adams, A. C. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2013.12.003 · Cited by 198
Sripetchwandee, J., Chattipakorn, N., & Chattipakorn, S. C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00496 · Cited by 199
Lack of Overt FGF21 Resistance in Two Mouse Models of Obesity and Insulin Resistance
Hale, C., Chen, M. M., Stanislaus, S., Chinookoswong, N., Hager, T., Wang, M., Véniant, M. M., & Xu, J. (2012) · Endocrinology · doi:10.1210/en.2010-1262 · Cited by 185
Self-citationJiang, S., Cheng, Y., Fang, Q., Shao, M., Zhang, Y., Liu, Y., Deng, Y., Shan, B., Liu, J., Li, H., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.565960 · Cited by 182
Ge, 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
Wu, A.-L., Kolumam, G., Stawicki, S., Chen, Y., Li, J., Zavala-Solorio, J., Phamluong, K., Feng, B., Li, L., Marsters, S., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002669 · Cited by 184
FGF19 subfamily members: FGF19 and FGF21
Dołęgowska, K., Marchelek‐Myśliwiec, M., Nowosiad-Magda, M., Sławiński, M., & Dołęgowska, B. (2019) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-019-00675-7 · Cited by 175
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
Going Back to the Biology of FGF21: New Insights
Lewis, J. E., Ebling, F. J. P., Samms, R. J., & Tsintzas, K. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.05.007 · Cited by 170
Hecht, R. I., Li, Y., Sun, J., Belouski, E., Hall, M. P., Hager, T., Yie, J., Wang, W., Winters, D., Smith, S. H., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049345 · Cited by 166
Self-citationFGF21-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
Mu, J., Pinkstaff, J. K., Li, Z., Skidmore, L. K., Li, N., Myler, H. A., Dallas-Yang, Q., Hays, A. A., Yao, J., Bussell, S., et al. (2011) · Diabetes · doi:10.2337/db11-0838 · Cited by 162
Wang, Q., Yuan, J., Yu, Z., Lin, L., Jiang, Y., Cao, Z., Zhuang, P., Whalen, M. J., Song, B., Wang, X., et al. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0663-7 · Cited by 157
Scarlett, J. M., Rojas, J. M., Matsen, M. E., Kaiyala, K. J., Stefanovski, D., Bergman, R. N., Hồng, N. T., Dorfman, M. D., Lantier, L., Wasserman, D. H., et al. (2016) · Nature Medicine · doi:10.1038/nm.4101 · Cited by 150
FGF21: A Novel Regulator of Glucose and Lipid Metabolism and Whole-Body Energy Balance
Szczepańska, E., & Gietka‐Czernel, M. (2022) · Hormone and Metabolic Research · doi:10.1055/a-1778-4159 · Cited by 155
Long-Acting FGF21 Has Enhanced Efficacy in Diet-Induced Obese Mice and in Obese Rhesus Monkeys
Véniant, M. M., Komorowski, R., Chen, P., Stanislaus, S., Winters, K., Hager, T., Zhou, L., Wada, R., Hecht, R. I., & Xu, J. (2012) · Endocrinology · doi:10.1210/en.2012-1211 · Cited by 148
Self-citationFGF21 reloaded: challenges of a rapidly growing field
Kharitonenkov, A., & Larsen, P. J. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.11.003 · Cited by 147
Kim, K. H., & Lee, M.-S. (2014) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2014.38.4.245 · Cited by 146
Metabolic Targets in Nonalcoholic Fatty Liver Disease
Esler, W. P., & Bence, K. K. (2019) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2019.04.007 · Cited by 145
FGF21 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
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
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
FGF21 Is an Exocrine Pancreas Secretagogue
Coate, K. C., Hernandez, G., Thorne, C. A., Sun, S., Le, T. D. V., Vale, K., Kliewer, S. A., & Mangelsdorf, D. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.004 · Cited by 136
Kim, H., Méndez, R., Zheng, Z., Chang, L., Cai, J., Zhang, R., & Zhang, K. (2014) · Endocrinology · doi:10.1210/en.2013-1490 · Cited by 134
Latest approaches for the treatment of obesity
Jackson, V. M., Breen, D. M., Fortin, J.-P., Liou, A., Kuzmiski, J. B., Loomis, A. K., Rives, M.-L., Shah, B., & Carpino, P. A. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.1044966 · Cited by 132
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
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
Brown adipocyte glucose metabolism: a heated subject
Hankir, M. K., & Klingenspor, M. (2018) · EMBO Reports · doi:10.15252/embr.201846404 · Cited by 130
Sa‐nguanmoo, P., Tanajak, P., Kerdphoo, S., Satjaritanun, P., Wang, X., Liang, G., Li, X., Jiang, C., Pratchayasakul, W., Chattipakorn, N., et al. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.08.006 · Cited by 122
Circulating FGF21 proteolytic processing mediated by fibroblast activation protein
Zhen, E. Y., Jin, Z., Ackermann, B. L., Thomas, M. K., & Gutierrez, J. A. (2016) · Biochemical Journal · doi:10.1042/bj20151085 · Cited by 123
FGF21 mediates the lipid metabolism response to amino acid starvation
De Sousa-Coelho, A. L., Relat, J., Hondares, E., Pérez-Martí, A., Ribas, F., Villarroya, F., Marrero, P. F., & Haro, D. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m033415 · Cited by 123
Huang, J., Ishino, T., Chen, G., Rolzin, P., Osothprarop, T. F., Retting, K., Li, L., Jin, P., Matin, M. J., Huyghe, B., et al. (2013) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.204420 · Cited by 121
Fibroblast growth factor 21: a regulator of metabolic disease and health span
Xie, T., & Leung, P. S. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00101.2017 · Cited by 121
Assini, J. M., Mulvihill, E. E., Burke, A. C., Sutherland, B. G., Telford, D. E., Chhoker, S. S., Sawyez, C. G., Drangova, M., Adams, A. C., Kharitonenkov, A., et al. (2015) · Endocrinology · doi:10.1210/en.2014-2003 · Cited by 119
Stanislaus, S., Hecht, R. I., Yie, J., Hager, T., Hall, M. P., Spahr, C. S., Wang, W., Weiszmann, J., Li, Y., Deng, L., et al. (2017) · Endocrinology · doi:10.1210/en.2016-1917 · Cited by 114
Self-citationSinghal, G., Fisher, F. M., Chee, M. J. S., Tan, T. G., Ouaamari, A. E., Adams, A. C., Najarían, R. M., Kulkarni, R., Benoist, C. O., Flier, J. S., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148252 · Cited by 112
FGF1 — 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
Separating mitogenic and metabolic activities of fibroblast growth factor 19 (FGF19)
Wu, X., Ge, H., Lemon, B. D., Vonderfecht, S. L., Baribault, H., Weiszmann, J., Gupte, J., Gardner, J., Lindberg, R. A., Wang, Z., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009427107 · Cited by 104
Self-citationMetabolic 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
Loss of hepatic PPARα promotes inflammation and serum hyperlipidemia in diet-induced obesity
Stec, D. E., Gordon, D. M., Hipp, J., Hong, S., Mitchell, Z. L., Franco, N. R., Robison, J., Anderson, C. D., Stec, D. F., & Hinds, T. D. (2019) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00153.2019 · Cited by 102
The FGF21–adiponectin axis in controlling energy and vascular homeostasis
Hui, X. H., Feng, T., Liu, Q., Gao, Y., & Xu, A. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw013 · Cited by 103
Fibroblast growth factor 21 night watch: advances and uncertainties in the field
Kharitonenkov, A., & DiMarchi, R. D. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12580 · Cited by 97
Yie, J., Wang, W., Deng, L., Tam, L., Stevens, J., Chen, M. M., Li, Y., Xu, J., Lindberg, R., Hecht, R., et al. (2012) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2012.01325.x · Cited by 99
Self-citationCold and Exercise: Therapeutic Tools to Activate Brown Adipose Tissue and Combat Obesity
da Silva, C. P. V., Hernández‐Saavedra, D., White, J. D., & Stanford, K. (2019) · Biology · doi:10.3390/biology8010009 · Cited by 102
Henriksson, E., & Andersen, B. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.601349 · Cited by 97
Fibroblast growth factor 21 is a metabolic regulator that plays a role in the adaptation to ketosis
Domouzoglou, E. M., & Maratos–Flier, E. (2011) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.001941 · Cited by 93
FGF21 in obesity and cancer: New insights
Lu, W., Li, X., & Luo, Y. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.11.026 · Cited by 93
Motamedi, S., Karimi, I., & Jafari, F. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-9997-0 · Cited by 86
Fibroblast Growth Factor 21 As an Emerging Therapeutic Target for Type 2 Diabetes Mellitus
So, W. Y., & Leung, P. S. (2016) · Medicinal Research Reviews · doi:10.1002/med.21390 · Cited by 85
Carson, B. P. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00097 · Cited by 86
FGF19 and FGF21: In NASH we trust
Talukdar, S., & Kharitonenkov, A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101152 · Cited by 82
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
Effect of Various Exercise Regimens on Selected Exercise-Induced Cytokines in Healthy People
Domin, R., Dadej, D., Pytka, M., Zybek-Kocik, A., Ruchała, M., & Guzik, P. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18031261 · Cited by 79
“FGF21 modulates metabolic adaptation to stress [117,121–123], decreases serum glucose and lipid concentrations, and improves insulin sensitivity [124,125].”
BackgroundLee, M. S., Choi, S., Ha, E. S., An, S.-Y., Kim, T. H., Han, S. J., Kim, H. J., Kim, D. J., KANG, Y. Y., & Lee, K. W. (2012) · Metabolism · doi:10.1016/j.metabol.2012.01.012 · Cited by 80
Fibroblast activation protein (FAP) as a novel metabolic target
Sanchez-Garrido, M. A., Habegger, K. M., Clemmensen, C., Holleman, C. L., Müller, T. D., Pérez–Tilve, D., Li, P., Agrawal, A., Finan, B., Drucker, D. J., et al. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.07.003 · Cited by 79
Thomas, D. T., DelCimmuto, N. R., Flack, K. D., Stec, D. E., & Hinds, T. D. (2022) · Antioxidants · doi:10.3390/antiox11020179 · Cited by 79
The roles of FGF21 and GDF15 in mediating the mitochondrial integrated stress response
Jena, J., García-Peña, L. M., & Pereira, R. O. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1264530 · Cited by 78
FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1
Kwon, M. M., O’Dwyer, S. M., Baker, R. K., Covey, S. D., & Kieffer, T. J. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.021 · Cited by 77
Araki, M., Nakagawa, Y., Oishi, A., Han, S., Wang, Y., Kumagai, K., Ohno, H., Mizunoe, Y., IWASAKI, H. O., Sekiya, M., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19072148 · Cited by 82
Goedeke, L., Perry, R. J., & Shulman, G. I. (2019) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104727 · Cited by 76
Jackson, T. C., & Kochanek, P. M. (2019) · Therapeutic Hypothermia and Temperature Management · doi:10.1089/ther.2019.0001 · Cited by 77
Omar, B. A., Andersen, B., Hald, J., Raun, K., Nishimura, E., & Åhrén, B. (2013) · Diabetes · doi:10.2337/db13-0710 · Cited by 76
Xiao, J., Bei, Y., Liu, J., Dimitrova‐Shumkovska, J., Kuang, D., Zhou, Q., Li, J., Yang, Y., Xiang, Y., Wang, F., et al. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12733 · Cited by 75
Fibroblast growth factor 21, the endocrine FGF pathway and novel treatments for metabolic syndrome
Zhang, J., & Li, Y. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.10.021 · Cited by 73
Self-citation
Metadata
- Authors
- Xu, J., Stanislaus, S., Chinookoswong, N., Lau, Y. Y., Hager, T., Patel, J., Ge, H., Weiszmann, J., Lu, S.-C., Graham, M., Busby, J., Hecht, R., Li, Y.-S., Li, Y., Lindberg, R., & Véniant, M. M.
- Affiliations
- Departments of1 Metabolic Disorders,
- Pharmacokinetics and Drug Metabolism, and
- Amgen (United States) (US)
- Protein Sciences, Amgen Inc., Thousand Oaks; and
- Corresponding author
- Xu, Jing
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2009-11
- Volume
- 297
- Issue
- 5
- Pages
- E1105-E1114
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2061333499
- Cited by
- 340
- References
- 28
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 17 · 2023: 21 · 2022: 30 · 2021: 22 · 2020: 22 · 2019: 28 · 2018: 22 · 2017: 29 · 2016: 23 · 2015: 14 · 2014: 23 · 2013: 16 · 2012: 19
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- FGF21, insulin resistance, glucose tolerance, insulin sensitivity, hepatic glucose production, adipose tissue, FGF signaling, ob/ob mice, diet-induced obesity, amylin, glucagon, hepatoma cells, adipocytes, glucose uptake
- MeSH terms
- Adipose Tissue, Animals, Cell Differentiation, Diet, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Fibroblast Growth Factors, Humans, Hypoglycemic Agents, Insulin Resistance, Islets of Langerhans, Liver, Liver Neoplasms, Experimental, Male, Mice, Inbred C57BL, Mice, Obese, Obesity, Recombinant Proteins, Blotting, Western, Glucose Clamp Technique, Adipocytes, Area Under Curve, 3T3-L1 Cells, Cell Line, Tumor, Mice, Islet Amyloid Polypeptide
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
