Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity
Abstract
OBJECTIVE: Fibroblast growth factor-21 (FGF21) is a novel endocrine and paracrine regulator of metabolic homeostasis. The aim of our study was to measure its serum concentrations in patients with obesity, obesity and type 2 diabetes mellitus (T2DM) and healthy subjects (C), and to assess the changes of its circulating levels and mRNA expression after dietary and pharmacological interventions. DESIGN: We measured biochemical parameters, serum FGF21, adiponectin, leptin and insulin levels by commercial ELISA and RIA kits, and mRNA expression in the liver, subcutaneous and visceral fat by RT PCR in 26 obese patients, 11 T2DM patients and 32 control subjects. The interventions were acute hyperinsulinaemia during isoglycaemic-hyperinsulinaemic clamp, very low calorie diet (VLCD) and 3 months treatment with PPAR-alpha agonist fenofibrate. RESULTS: Baseline serum FGF21 levels were significantly higher in both obese and T2DM patients relative to healthy controls. FGF21 levels in obesity did not significantly differ from T2DM group. Both 3 weeks of VLCD and 3 months of fenofibrate treatment significantly increased FGF21 levels. FGF21 mRNA expression in visceral fat was twofold higher in obesity relative to C group, while it did not differ in subcutaneous fat. VLCD significantly increased FGF21 mRNA expression in subcutaneous fat of obesity. 3-h hyperinsulinaemia during the clamp increased FGF21 levels in T2DM but not in C group. CONCLUSION: An increase in FGF21 levels after VLCD and fenofibrate treatment may contribute to positive metabolic effect of these interventions and suggests the possibility of direct positive metabolic effects of FGF21 in humans.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In humans, circulating FGF21 levels increase with obesity, type 2 diabetes, and NAFLD.
“In humans, circulating FGF21 levels also increase with obesity [[174], [175], [176]], type 2 diabetes [[176], [177], [178]], and NAFLD [179,180]”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [176]
Cites
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502 · see citing works
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · 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
Cellular signaling by fibroblast growth factor receptors
Eswarakumar, V. P., Lax, I., & Schlessinger, J. (2005) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.01.001 · Cited by 1,923 · see citing works
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 · 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
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 · see citing works
Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Lefebvre, P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27989 · Cited by 962 · 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
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 · see citing works
Adiponectin – journey from an adipocyte secretory protein to biomarker of the metabolic syndrome
TRUJILLO, M. E., & Scherer, P. E. (2005) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01426.x · Cited by 769 · 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
Tomlinson, E., Fu, L., John, L., Hultgren, B., Huang, X., Renz, M., Stephan, J. P., Tsai, S. P., Powell-Braxton, L., French, D., et al. (2002) · Endocrinology · doi:10.1210/endo.143.5.8850 · Cited by 576 · see citing works
Havel, P. J. (2002) · Current Opinion in Lipidology · doi:10.1097/00041433-200202000-00008 · Cited by 575 · see citing works
Wente, W., Efanov, A. M., Brenner, M. B., Kharitonenkov, A., Koster, A. M., Sandusky, G. E., Sewing, S., Treinies, I., Zitzer, H., & Gromada, J. (2006) · Diabetes · doi:10.2337/db05-1435 · Cited by 497 · see citing works
PPARα is a key regulator of hepatic FGF21
Lundåsen, T., Hunt, M., Nilsson, L.-M., Sanyal, S., Angelin, B., Alexson, S., & Rudling, M. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.06.068 · Cited by 361 · see citing works
Muise, E. S., Azzolina, B., Kuo, D. W., El-Sherbeini, M., Tan, Y., Yuan, X., Mu, J., Thompson, J. R., Berger, J. P., & Wong, K. K. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.044826 · Cited by 294 · see citing works
Housa, D., Housova, J., Vernerová, Z., & Haluzı́k, M. (2006) · Physiological Research · doi:10.33549/physiolres.930848 · Cited by 264 · see citing works
Molecular determinants of FGF‐21 activity—synergy and cross‐talk with PPARγ signaling
Moyers, J. S., Shiyanova, T. L., Mehrbod, F., Dunbar, J. D., Noblitt, T. W., Otto, K. A., Reifel-Miller, A. E., & Kharitonenkov, A. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20847 · Cited by 193 · see citing works
Chen, W.-W., Li, L., Yang, G.-Y., Li, K., Qi, X.-Y., Zhu, W., Tang, Y., Liu, H., & Boden, G. (2007) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2007-985148 · Cited by 186 · see citing works
Plasma Concentrations of Fibroblast Growth Factors 19 and 21 in Patients with Anorexia Nervosa
Dostálová, I., Kaválková, P., Haluzíková, D., Lacinová, Z., Mráz, M., Papežová, H., & Haluzı́k, M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0746 · Cited by 111 · see citing works
Fibroblast Growth Factor-21 as a Therapeutic Agent for Metabolic Diseases
Kharitonenkov, A., & Shanafelt, A. B. (2008) · BioDrugs · doi:10.2165/00063030-200822010-00004 · Cited by 98 · see citing works
The endocrine profile of subcutaneous and visceral adipose tissue of obese patients
Dolinkova, M., Dostálová, I., Lacinová, Z., Michalský, D., Haluzíková, D., Mráz, M., Kasalicky, M., & Haluzı́k, M. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.05.001 · Cited by 89 · see citing works
Anderlová, K., Doležalová, R., Housova, J., Bošanská, L., Haluzíková, D., Křemen, J., Škrha, J., & Haluzı́k, M. (2007) · Physiological Research · doi:10.33549/physiolres.931058 · Cited by 43 · see citing works
Fu, X.-B. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i24.3590 · Cited by 40 · see citing works
The role of resistin in obesity-induced insulin resistance.
Haluzı́k, M., & Haluzíková, D. (2006) · PubMed · Cited by 39 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529 · see citing works
“However, numerous additional studies have found detectable FGF21 mRNA expression in visceral WAT (157, 158), subcutaneous WAT (145, 157, 158), epicardial WAT (159), cervical adipose tissue (160, 161), and PVAT (162, 163), with the latter two depots containing both WAT and BAT.”
BackgroundBasic Mechanisms of Diabetic Heart Disease
Ritchie, R. H., & Abel, E. D. (2020) · Circulation Research · doi:10.1161/circresaha.120.315913 · Cited by 730 · see citing works
Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease
Itoh, N., & Ornitz, D. M. (2010) · The Journal of Biochemistry · doi:10.1093/jb/mvq121 · Cited by 708 · see citing works
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 · see citing works
“Another group found an increase in serum FGF21 levels in obese individuals who followed a very low calorie diet for 3 months (16).”
BackgroundInfluentialEndocrine 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
Suomalainen, A., Elo, J. M., Pietiläinen, K. H., Hakonen, A. H., Sevastianova, K., Korpela, M., Isohanni, P., Marjavaara, S. K., Tyni, T., Kiuru-Enari, S., et al. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70155-7 · Cited by 427 · 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
Fibroblast Growth Factor 21 as an emerging metabolic regulator: clinical perspectives
Woo, Y. C., Xu, A., Wang, Y., & Lam, K. S. L. (2012) · Clinical Endocrinology · doi:10.1111/cen.12095 · Cited by 302 · see citing works
Sarruf, D. A., Thaler, J. P., Morton, G. J., German, J. P., Fischer, J. D., Ogimoto, K., & Schwartz, M. W. (2010) · Diabetes · doi:10.2337/db09-1878 · Cited by 287 · 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
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
Hepatokines and metabolism: Deciphering communication from the liver
Jensen-Cody, S. O., & Potthoff, M. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101138 · Cited by 252 · see citing works
Interplay between FGF21 and insulin action in the liver regulates metabolism
Emanuelli, B., Vienberg, S. G., Smyth, G., Cheng, C., Stanford, K. I., Arumugam, M., Michael, M. D., Adams, A. C., Kharitonenkov, A., & Kahn, C. R. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67353 · Cited by 243 · see citing works
“FGF21 expression is also induced by endogenous PPAR α ligands such as fatty acids, which increase after prolonged fasting (14), by a ketogenic diet in mice (9), or by fibrates, which are artificial PPAR α ligands (11, 15).”
Itoh, N. (2010) · Cell and Tissue Research · doi:10.1007/s00441-010-1024-2 · Cited by 247 · see citing works
“Fgf21 Serum Fgf21 levels are increased in patients with type 2 diabetes and obesity (Table 2) (Zhang et al 2008; Chen et al 2008; Mraz et al 2009).”
BackgroundFGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders
Lehtonen, J. M., Forsström, S., Bottani, E., Viscomi, C., Baris, O. R., Isoniemi, H., Höckerstedt, K., Österlund, P., Hurme, M., Jylhävä, J., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003374 · Cited by 220 · see citing works
Mashili, F. L., Austin, R. L., Deshmukh, A. S., Fritz, T., Caidahl, K., Bergdahl, K., Zierath, J. R., Chibalin, A., Moller, D. E., Kharitonenkov, A., et al. (2011) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.1177 · Cited by 222 · 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
“Circulating levels of FGF21 are significantly elevated in humans during pathophysiological states, including type 2 diabetes (16, 18), obesity (22, 30, 93), hepatosteatosis (30, 79, 146), pancreatitis (117, 137), and mitochondrial dysfunction (78).”
BackgroundFGF21 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 · see citing works
“Two commercial kits are commonly used to measure total FGF21 in human plasma, one from R&D Systems (Vendor A) and the other from Biovendor (Vendor B) (Bobbert et al., 2013; Hanssen et al., 2015; Mraz et al., 2009; Zhang et al., 2008).”
MethodMetabolic 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
FGF21 as a Hepatokine, Adipokine, and Myokine in Metabolism and Diseases
Itoh, N. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00107 · Cited by 198 · see citing works
“Serum FGF21 levels were also significantly higher in patients with both obesity and type 2 diabetes (29), in mitochondria disease patients with dysfunctional mitochondria (30), in Cushing’s syndrome patients with prolonged and inappropriately high levels of glucocorticoids (31), and in preeclampsia patients with serio…”
BackgroundInventing new medicines: The FGF21 story
Kharitonenkov, A., & Adams, A. C. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2013.12.003 · Cited by 198 · see citing works
“Subsequent studies demonstrated that FGF21 represented a secreted factor which was controlled by important metabolic pathways such as PPARγ [9] and PPARα [10,11].”
BackgroundIncreased serum FGF21 levels in patients with nonalcoholic fatty liver disease
Yilmaz, Y. N., Eren, F., Yönal, O., Kurt, R., Aktaş, B., Çelikel, Ç., Özdogan, O. C., İmeryüz, N., Kalaycı, C., & Avşar, E. (2010) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2010.02338.x · Cited by 196 · see citing works
Chow, W. S., Xu, A., Woo, Y. C., Tso, A. W. K., Cheung, S., Fong, C. H.-Y., Tse, H., Chau, M. T., Cheung, B. M. Y., & Lam, K. S. L. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.301599 · Cited by 193 · see citing works
“In obese subjects, both serum FGF21 levels and visceral fat FGF21 mRNA expression were significantly higher compared with that of lean subjects.(9) Of note, our study cohort was overweighed with a mean body mass index of almost 25 kg/m(2) and a high central obesity prevalence of 43.”
BackgroundFu, T., Seok, S., Choi, S.-E., Huang, Z., Suino-Powell, K., Xu, H., Kemper, B., & Kemper, J. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00596-14 · Cited by 187 · see citing works
“Notably, circulating FGF21 levels are highly elevated in obese individuals with metabolic syndrome (37), suggesting that FGF21 signaling might be impaired in obesity (32), but FGF21 resistance in obesity has been controversial in mouse studies (16, 32, 38).”
BackgroundMirza, M. A. I., Alsiö, J., Hammarstedt, A., Erben, R. G., Michaëlsson, K., Tivesten, Å., Marsell, R., ORWOLL, E. S., Karlsson, M. K., Ljunggren, Ö., et al. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.214619 · Cited by 181 · see citing works
High 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
“CONCLUSIONS—Previous studies have demonstrated that circulating FGF21 levels are elevated in obesity and its relatedmetabolic disorders, including insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease (4,6,7,12).”
Lin, Z., Wu, Z., Yin, X., Liu, Y., Yan, X., Lin, S., Xiao, J., Wang, X., Feng, W., & Li, X. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015534 · Cited by 179 · see citing works
“metabolic syndrome or type 2 diabetes [18,19] and are closely associated with obesity [18,20] and renal dysfunction in chronic hemodialysis [21].”
BackgroundLi, H., Wu, G., Fang, Q., Zhang, M., Hui, X., Sheng, B., Wu, L., Bao, Y., Li, P., Xu, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02677-9 · Cited by 178 · see citing works
Yu, 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
Gómez‐Ambrosi, J., Gallego-Escuredo, J. M., Catalán, V., Rodrı́guez, A., Domingo, P., Moncada, R., Valentí, V., Salvador, J., Giralt, M., Villarroya, F., et al. (2016) · Clinical Nutrition · doi:10.1016/j.clnu.2016.04.027 · Cited by 168 · see citing works
“However, studies including obese patients encompassing different degrees of insulin resistance (normoglycemia, IGT and T2D) are controversial [29,34,35].”
BackgroundReinehr, T., Woelfle, J., Wunsch, R., & Roth, C. L. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1221 · Cited by 160 · see citing works
“One study in obese adults also reported a decrease of FGF-21 levels in weight loss (14), whereas two other adult studies did not find a significant change of FGF-21 due to weight loss (33, 34).”
BackgroundResultDeterminants of GH resistance in malnutrition
Fazeli, P. K., & Klibanski, A. (2013) · Journal of Endocrinology · doi:10.1530/joe-13-0477 · Cited by 158 · see citing works
“In humans, a very low-calorie diet and prolonged fasting result in increased levels of FGF21 (Galman et al. 2008, Mraz et al. 2009).”
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
“Because FGF21 expression can be augmented by fenofibrate in humans (17, 20, 45), we predict that FAP inhibition would synergize with fenofibrate or other agonists for peroxisome proliferator-activated receptor , much like the way DPPIV inhibitors synergize with metformin, which increases the level of total GLP-1 (Fig.”
BackgroundFibroblast growth factor-21, energy balance and obesity
Giralt, M., Gavaldà‐Navarro, A., & Villarroya, F. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.09.018 · Cited by 146 · see citing works
FGF21 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 · see citing works
Next generation plasma proteome profiling to monitor health and disease
Zhong, W., Edfors, F., Gummesson, A., Bergström, G. M. L., Fagerberg, L., & Uhlén, M. (2021) · Nature Communications · doi:10.1038/s41467-021-22767-z · Cited by 137 · see citing works
Liu, J., Xu, Y., Hu, Y., & Wang, G. (2014) · Metabolism · doi:10.1016/j.metabol.2014.11.009 · Cited by 137 · see citing works
“[75] Mraz M, Bartlova M, Lacinova Z, Michalsky D, Kasalicky M, Haluzikova D, et al.”
BackgroundAdditive relationship between serum fibroblast growth factor 21 level and coronary artery disease
Shen, Y., Ma, X., Zhou, J., Pan, X., Hao, Y., Zhou, M., Lu, Z., Gao, M., Bao, Y., & Jia, W. (2013) · Cardiovascular Diabetology · doi:10.1186/1475-2840-12-124 · Cited by 135 · see citing works
“reported that serum FGF21 level becomes elevated under conditions of insulin resistance [15], and An et al.”
BackgroundLin, Z., Zhou, Z., Liu, Y., Gong, Q., Yan, X., Xiao, J., Wang, X., Lin, S., Feng, W., & Li, X. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018398 · Cited by 129 · see citing works
“Human studies indicate that circulating levels of FGF21 increased in obese individuals [18], subjects with metabolic syndrome, type 2 diabetes mellitus[19–21] and coronary heart disease[22].”
BackgroundFibroblast Growth Factor 21 (FGF21) in Human Cerebrospinal Fluid
Tan, B. K., Hallschmid, M., Adya, R., Kern, W., Lehnert, H., & Randeva, H. S. (2011) · Diabetes · doi:10.2337/db11-0672 · Cited by 129 · see citing works
“We report significantly higher circulating FGF21 levels in obese compared with lean subjects, in agreement with previous studies (12,17).”
Novel Insights into the Cardio-Protective Effects of FGF21 in Lean and Obese Rat Hearts
Patel, V., Adya, R., Chen, J., Ramanjaneya, M., Bari, M. F., Bhudia, S. K., Hillhouse, E. W., Tan, B. K., & Randeva, H. S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087102 · Cited by 124 · see citing works
“Notably, the hepatokine/ adipokine FGF21, circulating levels of which are elevated in obesity and type 2 diabetes [10,11], has been implicated as a key metabolic regulator.”
BackgroundCirculating 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
Fibroblast Growth Factor 21 Predicts the Metabolic Syndrome and Type 2 Diabetes in Caucasians
Bobbert, T., Schwarz, F., Fischer‐Rosinsky, A., Pfeiffer, A. F. H., Möhlig, M., Mai, K., & Spranger, J. (2012) · Diabetes Care · doi:10.2337/dc12-0703 · Cited by 125 · see citing works
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 · see citing works
Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy
Itoh, N., Ohta, H., & Konishi, M. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00154 · Cited by 119 · see citing works
Haluzíková, D., Lacinová, Z., Kaválková, P., Drápalová, J., Křížová, J., Bártlová, M., Mráz, M., Petr, T., Vı́tek, L., Kasalicky, M., et al. (2013) · Obesity · doi:10.1002/oby.20208 · Cited by 118 · see citing works
“Subcutaneous adipose tissue samples for mRNA expression analysis from a subset of control women (n 1⁄4 10) and a subset of obese women (n 1⁄4 13) before LSG and at 6, 12, and 24 months after surgery (n 1⁄4 8) were obtained from the abdominal region using single fine-needle biopsy as described in detail elsewhere (24).”
BackgroundMethodResultInfluentialFibroblast growth factors in cardiovascular disease: The emerging role of FGF21
Domouzoglou, E. M., Naka, K. Κ., Vlahos, A. P., Papafaklis, M. I., Michalis, L. K., Tsatsoulis, A., & Maratos–Flier, E. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00527.2015 · Cited by 115 · see citing works
“Baseline FGF21 serum levels are significantly higher in obese people and patients with type 2 diabetes compared with controls, and treatment with fenofibrate further increases these levels (78, 85).”
BackgroundZhang, C., Huang, Z., Gu, J., Yan, X., Lu, X., Zhou, S., Wang, S., Shao, M., Zhang, F., Cheng, P., et al. (2015) · Diabetologia · doi:10.1007/s00125-015-3630-8 · Cited by 113 · see citing works
“It has been predominantly investigated in the liver and adipose tissue [10].”
BackgroundIglesias, P., Selgas, R., Romero, S., & Díez, J. J. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0357 · Cited by 113 · see citing works
So, W. Y., Cheng, Q., Chen, L., Evans‐Molina, C., Xu, A., Lam, K. S. L., & Leung, P. S. (2013) · Diabetes · doi:10.2337/db13-0645 · Cited by 109 · see citing works
“To test this hypothesis, the action of FGF21 on pancreatic islets throughout progression to T2DM in diabetic db/db and lean mice was examined.”
BackgroundInfluentialATF4- and CHOP-Dependent Induction of FGF21 through Endoplasmic Reticulum Stress
Wan, X., Lu, X., Xiao, Y.-C., Lin, Y., Zhu, H., Ding, T., Yang, Y., Huang, Y., Zhang, Y., Liu, Y., et al. (2014) · BioMed Research International · doi:10.1155/2014/807874 · Cited by 105 · see citing works
“Circulating FGF21 levels were significantly higher in overweight subjects than those in lean individuals [20, 21].”
BackgroundFGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases
Sonoda, J., Chen, M. Z., & Baruch, A. (2017) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2017-0002 · Cited by 106 · see citing works
Glucocorticoids Regulate the Metabolic Hormone FGF21 in a Feed-Forward Loop
Patel, R., Bookout, A. L., Magomedova, L., Owen, B. M., Consiglio, G. P., Shimizu, M., Zhang, Y., Mangelsdorf, D. J., Kliewer, S. A., & Cummins, C. L. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1259 · Cited by 102 · see citing works
Distinct Changes in Serum Fibroblast Growth Factor 21 Levels in Different Subtypes of Diabetes
Xiao, Y., Xu, A., Law, L. S., Chen, C., Li, H., Li, X., Yang, L., Liu, S., Zhou, Z., & Lam, K. S. L. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1930 · Cited by 102 · see citing works
“Despite the multiple salutatory effects of FGF21 on glucose and lipid metabolism in animals, circulating FGF21 levels are elevated in obesity (2) and patients with type 2 diabetes mellitus (3, 4), dyslipidemia (2, 5), impaired glucose tolerance (3), nonalcoholic fatty liver disease (6), and coronary heart disease (7).”
BackgroundQin, Y., Zhou, Y. G., Chen, S., Zhao, X.-L., Ran, L., Zeng, X.-L., Wu, Y., Chen, J., Kang, C., Shu, F., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133496 · Cited by 101 · see citing works
“adiponetin levels were negatively associated with serum FGF21 levels in both obese and T2DM patients [39].”
BackgroundZhang, C., Shao, M., Yang, H., Chen, L., Yu, L., Cong, W., Tian, H., Zhang, F., Cheng, P., Jin, L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082275 · Cited by 100 · see citing works
“To date, the study of FGF21 has focused on its effects in liver and adipose tissue [22]; kidney has relatively low levels of FGF21 [23].”
BackgroundBergmann, K., & Sypniewska, G. (2012) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2012-0490 · Cited by 96 · see citing works
Giannini, C., Feldstein, A. E., Santoro, N., Kim, G. J., Kursawe, R., Pierpont, B. M., & Caprio, S. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1250 · Cited by 95 · see citing works
Emerging role of fibroblast growth factors 15/19 and 21 as metabolic integrators in the liver
Cicione, C., Degirolamo, C., & Moschetta, A. (2012) · Hepatology · doi:10.1002/hep.25929 · Cited by 95 · see citing works
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 · see citing works
“It was also reported that obese patients had increased FGF21 blood concentrations, whereas FGF21 mRNA expression in visceral fat increased 2-fold in obese patients compared with in control subjects, and a very low–calorie diet induced a significant increase of FGF21 mRNA expression in the subcutaneous fat of obese pat…”
BackgroundTargeting FGF21 for the Treatment of Nonalcoholic Steatohepatitis
Zarei, M., Pizarro‐Delgado, J., Barroso, E., Palomer, X., & Vázquez‐Carrera, M. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.12.005 · Cited by 92 · see citing works
FGF21: a novel prospect for the treatment of metabolic diseases.
Kharitonenkov, A., & Shanafelt, A. B. (2009) · PubMed · Cited by 91 · see citing works
Fibroblast Growth Factor-21 May Mediate Growth Hormone Resistance in Anorexia Nervosa
Fazeli, P. K., Misra, M., Goldstein, M. A., Miller, K. K., & Klibanski, A. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1730 · Cited by 90 · see citing works
Plasma FGF21 Is Elevated by the Intense Lipid Mobilization of Lactation
Schoenberg, K. M., Giesy, S. L., Harvatine, K. J., Waldron, M. R., Cheng, C., Kharitonenkov, A., & Boisclair, Y. R. (2011) · Endocrinology · doi:10.1210/en.2011-1425 · Cited by 90 · see citing works
“So for these tissues, cattle resemble humans who have low expression in WAT (46, 48) and mostly undetectable expression in skeletal muscle (49).”
BackgroundMurata, Y., Konishi, M., & Itoh, N. (2011) · Journal of Nutrition and Metabolism · doi:10.1155/2011/981315 · Cited by 85 · see citing works
“Serum FGF21 levels are increased in patients with type 2 diabetes, gestational diabetes, and obesity, indicating FGF21 to be a potential new marker in patients with type 2 diabetes (Table 1) [66–71].”
BackgroundFGF 21 deletion exacerbates diabetic cardiomyopathy by aggravating cardiac lipid accumulation
Yan, X., Chen, J., Zhang, C., Zhou, S., Zhang, Z., Chen, J., Feng, W., Li, X., & Tan, Y. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12530 · Cited by 85 · see citing works
“To date, the function of FGF21 has been extensively investigated, but most studies focused on the liver, adipose tissue [20] and skeletal muscle [10, 16].”
BackgroundLee, Y., Lim, S. K., Hong, E. S., Kim, J. H., Moon, M. K., Chun, E. J., Choi, S. I., Kim, Y., Park, Y. J., Park, K. S., et al. (2012) · Clinical Endocrinology · doi:10.1111/cen.12134 · Cited by 84 · see citing works
Crujeiras, A. B., Gómez-Arbeláez, D., Zulet, M. Á., Carreira, M. C., Sajoux, I., de Luis, D. A., Castro, A. I., Baltar, J., de la Torre, I. B., Sueiro, A. M., et al. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.138 · Cited by 83 · see citing works
Ong, K. L., Rye, K., O'Connell, R. L., Jenkins, A. J., Brown, C. S. B., Xu, A., SULLIVAN, D. R., Barter, P. J., KEECH, A. C., & on behalf of the FIELD study investigators (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2267 · Cited by 82 · see citing works
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 82 · see citing works
“Treating newly diagnosed T2DM patients for 12 weeks with metformin led to decreased FGF21 levels [102].”
BackgroundInfluentialObesity as the common soil of non‐alcoholic fatty liver disease and diabetes: Role of adipokines
Hui, E., Xu, A., Yang, H. B., & Lam, K. S. L. (2013) · Journal of Diabetes Investigation · doi:10.1111/jdi.12093 · Cited by 79 · see citing works
Serum levels of fibroblast growth factor‐21 are increased in chronic and acute renal dysfunction
Hindricks, J., Ebert, T., Bachmann, A., Kralisch, S., Lössner, U., Kratzsch, J., Stolzenburg, J., Dietel, A., Beige, J., Anders, M. S., et al. (2013) · Clinical Endocrinology · doi:10.1111/cen.12380 · Cited by 79 · see citing works
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 · see citing works
Xiao, Y., Liu, L., Xu, A., Zhou, P., Long, Z., Tu, Y., Chen, X., Tang, W., Huang, G., & Zhou, Z. (2015) · Cardiovascular Diabetology · doi:10.1186/s12933-015-0229-9 · Cited by 75 · see citing works
“FGF21 mRNA expression was shown to be 1fold higher in subcutaneous adipose tissue than in visceral adipose tissue in subjects with a BMI < 40 kg/m(2), whereas in subjects with a BMI > 40 kg/m(2), FGF21 mRNA expression was similar in both tissues [5].”
BackgroundWang, D., Zhu, W., Jie-ming, L., An, C., & Wang, Z. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081190 · Cited by 73 · see citing works
“In contrast, increased concentrations of serum FGF21 have been found in subjects with T2DM and in obese children and adults [22,23].”
BackgroundResultSemba, R. D., Sun, K., Egan, J. M., Crasto, C., Carlson, O. D., & Ferrucci, L. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2823 · Cited by 70 · see citing works
Fibroblast Growth Factor 21 Analogs for Treating Metabolic Disorders
Zhang, J., & Li, Y. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00168 · Cited by 70 · see citing works
“The avimer fusion molecule, FGF21 (1-171)-WD22, indeed has improved properties and decreased susceptibility to modifications compared to wild-type FGF21 (78), providing a novel framework for further engineering that is not possible with the wild-type protein.”
BackgroundZhang, W., Chu, S., Ding, W., & Wang, F. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129791 · Cited by 70 · see citing works
“Human studies have indicated that serum levels of FGF21 were increased in obese people and in people with metabolic syndrome or diabetes mellitus [3,4].”
BackgroundNygaard, E., Møller, C. L., Kievit, P., Grove, K. L., & Andersen, B. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.79 · Cited by 69 · see citing works
Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology
Li, H., Zhang, J., & Jia, W. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0244-8 · Cited by 69 · see citing works
“Interestingly, circulating FGF21 concentrations are increased in human subjects who either are overweight or have type 2 diabetes, impaired glucose tolerance, or nonalcoholic fatty liver disease [45–52].”
BackgroundFGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue
Markan, K. R., Naber, M. C., Small, S. M., Peltekian, L., Kessler, R. L., & Potthoff, M. J. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.03.009 · Cited by 68 · see citing works
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 67 · see citing works
Lips, M. A., de Groot, G. H., Berends, F. J., Wiezer, M. J., van Wagensveld, B. A., Swank, D. J., Luijten, A. A. P. M., van Dijk, K. W., Pijl, H., Jansen, P. L. M., et al. (2014) · Clinical Endocrinology · doi:10.1111/cen.12496 · Cited by 65 · see citing works
Lehtonen, J. M., Auranen, M., Darín, N., Sofou, K., Bindoff, L. A., Hikmat, O., Uusimaa, J., Vieira, P., Tulinius, M., Lönnqvist, T. R. I., et al. (2020) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12307 · Cited by 64 · see citing works
“Both cytokines are induced in mice and humans with mitochondrial myopathy, but also in some nonmitochondrial metabolic (FGF21) and degenerative/endstage (GDF15) conditions.(25,26) However, in the case of FGF21, mitochondrial myopathy is the only condition, in which secretion of FGF21 is directly linked to a monogenic…”
BackgroundCardiac actions of fibroblast growth factor 23
Faul, C. (2016) · Bone · doi:10.1016/j.bone.2016.10.001 · Cited by 63 · see citing works
Metabolic role of fibroblast growth factor 21 in liver, adipose and nervous system tissues
Lin, X., Liu, Y. B., & Hu, H. (2017) · Biomedical Reports · doi:10.3892/br.2017.890 · Cited by 61 · see citing works
“The browning and thermogenesis of WAT reveal the important regulatory effect of FGF21 on the energy metabolism and body weight of the mice.”
InfluentialTyynismaa, H., Raivio, T., Hakkarainen, A., Ortega‐Alonso, A., Lundbom, N. M. I., Kaprio, J. A., Rissanen, A., Suomalainen, A., & Pietiläinen, K. H. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1326 · Cited by 61 · see citing works
Liu, J., Foo, J. P., Liu, S., & Lim, S. C. (2015) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2015.02.032 · Cited by 58 · see citing works
“[12].”
BackgroundPhysiological modulation of circulating FGF21: relevance of free fatty acids and insulin
Mai, K., Bobbert, T., Groth, C., Aßmann, A., Meinus, S., Kraatz, J., Andres, J., Arafat, A. M., Pfeiffer, A. F. H., Möhlig, M., et al. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00020.2010 · Cited by 58 · see citing works
“Such a variable effect of insulin on FGF-21 levels in obese and lean subjects was recently suggested by Mraz and colleagues (20), who observed unchanged FGF-21 levels during hyperinsulinemic clamp in lean subjects, whereas an insulin-induced increase in FGF-21 was found in obese subjects.”
BackgroundResultRelation between fibroblast growth factor–21, adiposity, metabolism, and weight reduction
Mai, K., Schwarz, F., Bobbert, T., Andres, J., Aßmann, A., Pfeiffer, A. F. H., & Spranger, J. (2010) · Metabolism · doi:10.1016/j.metabol.2010.02.016 · Cited by 58 · see citing works
“In accordance to recent data, we observed comparable circulating FGF-21 levels in obese subjects with and without diabetes [7].”
BackgroundResultInfluentialDynamic Change of Serum FGF21 Levels in Response to Glucose Challenge in Human
Lin, Z., Gong, Q., Wu, C., Yu, J., Lü, T., Pan, X., Lin, S., & Li, X. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1132 · Cited by 58 · see citing works
“Previous studies in different ethnic groups have consistently demonstrated increased concentrations of circulating FGF21 in diabetes subjects (3, 4, 11).”
BackgroundDing, P., Yang, R., Li, C., Fu, H., Ren, G.-L., Wang, P., Zheng, D., Chen, W., Yang, L., Mao, Y., et al. (2023) · Critical Care · doi:10.1186/s13054-023-04488-5 · Cited by 57 · see citing works
“Previous studies have shown significantly elevated levels of FGF21 in patients with type 2 diabetes, nonalcoholic fatty liver and obesity [32, 33].”
BackgroundIncreased Placental Expression of Fibroblast Growth Factor 21 in Gestational Diabetes Mellitus
Nitert, M. D., Barrett, H. L., Kubala, M. H., Scholz‐Romero, K., Denny, K. J., Woodruff, T. M., McIntyre, D. H., & Callaway, L. K. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2581 · Cited by 57 · see citing works
Fletcher, J. A., Meers, G. M.-E., Laughlin, M. H., Ibdah, J. A., Thyfault, J. P., & Rector, R. S. (2012) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h2012-091 · Cited by 53 · see citing works
“However, hepatic FGF-21 mRNA expression in the liver is 100 times higher than that observed in adipose tissue (Mraz et al. 2009), and hepatic expression is further elevated with obesity (Fisher et al. 2010).”
BackgroundResultDomingo, P., Gallego-Escuredo, J. M., Domingo, J. C., Gutiérrez, M. D. M., Mateo, G. M., Fernández, I., Vidal, F., Giralt, M., & Villarroya, F. (2010) · AIDS · doi:10.1097/qad.0b013e3283400088 · Cited by 53 · see citing works
“Some studies have indicated that FGF21 is expressed in human adipose tissue [16,17] thus it may be that lipoatrophic subcutaneous fat or the enlarged visceral adipose tissue depots are sources of increased FGF21 levels.”
BackgroundResultLi, Q., Zhang, Y., Ding, D., Yang, Y., Chen, Q., Su, D., Chen, X., Yang, W., Qiu, J., & Ling, W. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2308 · Cited by 52 · see citing works
The regulation of FGF21 gene expression by metabolic factors and nutrients
Erickson, A., & Moreau, R. F. (2016) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2016-0016 · Cited by 50 · see citing works
Zarei, M., Aguilar-Recarte, D., Palomer, X., & Vázquez‐Carrera, M. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154342 · Cited by 49 · see citing works
Bužga, M., Machytka, E., Klvaňa, P., Kupka, T., Zavadilová, V., Zonča, P., & Švagera, Z. (2014) · Obesity Surgery · doi:10.1007/s11695-014-1191-4 · Cited by 47 · see citing works
“humans, increased FGF21 levels are associated with obesity in both children [34] and adults [35, 36], indicating a connection between FGF21 and body fat mass.”
BackgroundNonogaki, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031600 · Cited by 46 · see citing works
- Authors
- Mraz, M., Bartlova, M., Lacinova, Z., Michalsky, D., Kasalicky, M., Haluzikova, D., Matoulek, M., Dostalova, I., Humenanska, V., & Haluzik, M.
- ORCID
- Matoulek, M.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2009-08-14
- Volume
- 71
- Issue
- 3
- Pages
- 369-375
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2157891550
- Cited by
- 279
- References
- 27
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 12 · 2023: 17 · 2022: 14 · 2021: 19 · 2020: 19 · 2019: 17 · 2018: 13 · 2017: 18 · 2016: 15 · 2015: 26 · 2014: 27 · 2013: 16 · 2012: 21
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Rheumatology › GDF15 and Related Biomarkers
- Keywords
- FGF21, type 2 diabetes, obesity, visceral adipose tissue, subcutaneous adipose tissue, liver, very low calorie diet, fenofibrate, PPARα agonist, hyperinsulinemic-euglycemic clamp, adiponectin, leptin, insulin, metabolic homeostasis
- MeSH terms
- Adult, Diabetes Mellitus, Type 2, Female, Fibroblast Growth Factors, Humans, Liver, Middle Aged, Obesity, Fenofibrate, Gene Expression, Case-Control Studies, Leptin, Adiponectin
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
