Cited by 279Fibroblast Growth Factor ResearchAdipokines, Inflammation, and Metabolic DiseasesGDF15 and Related Biomarkers

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Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity

Mraz, M., Bartlova, M., Lacinova, Z., Michalsky, D., Kasalicky, M., Haluzikova, D., Matoulek, M., Dostalova, I., Humenanska, V., Haluzik, M.·2009·Clinical Endocrinology

DOI 10.1111/j.1365-2265.2008.03502.x

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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.

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Homeostasis model assessment: insulin resistance and ?-cell function from fasting plasma glucose and insulin concentrations in man
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Sandoval, V., Femenias, A., Martínez‐Garza, Ú., Sanz‐Lamora, H., Castagnini, J. M., Quifer‐Rada, P., Lamuela-Raventós, R. M., Marrero, P. F., Haro, D., & Relat, J. (2019) · Antioxidants · doi:10.3390/antiox8090360 · Cited by 46
“It has been widely described that FGF21 levels are increased in obesity and diabetes in both animal models and humans [60,103,104].”
Background
FGF21 Response to Critical Illness: Effect of Blood Glucose Control and Relation With Cellular Stress and Survival
Thiessen, S., Vanhorebeek, I., Derese, I., Gunst, J., & den Berghe, G. V. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2700 · Cited by 45
“The sample size of the human study allowed at least 80% statistical power to detect, with 95% certainty, a doubling of serum FGF21 concentrations in critically ill patients as compared with control subjects, an effect size comparable to that observed in diabetes (9).”
BackgroundResult
Bitter melon extract attenuating hepatic steatosis may be mediated by FGF21 and AMPK/Sirt1 signaling in mice
Yu, Y., Zhang, X. H., Ebersole, B., Ribnicky, D., & Wang, Z. Q. (2013) · Scientific Reports · doi:10.1038/srep03142 · Cited by 46
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Fibroblast Growth Factor 21 and Thyroid Hormone Show Mutual Regulatory Dependency but Have Independent Actions In Vivo
Domouzoglou, E. M., Fisher, F. M., Astapova, I. I., Fox, E. C., Kharitonenkov, A., Flier, J. S., Hollenberg, A. N., & Maratos–Flier, E. (2014) · Endocrinology · doi:10.1210/en.2013-1902 · Cited by 41
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“Although obesity is known to be associated with elevated circulating FGF21 level in humans (4, 5, 27), the association between body fat distribution and the FGF21 level has not Figure 1.”
Background
Fibroblast growth factor 21 in chronic kidney disease
Anuwatmatee, S., Tang, S., Wu, B. J., Rye, K., & Ong, K. L. (2017) · Clinica Chimica Acta · doi:10.1016/j.cca.2017.11.002 · Cited by 40
FGF21 and Chronic Kidney Disease.
Salgado, J., Goes, M. A., & Salgado, N. (2021) · Metabolism: Clinical and Experimental · doi:10.1016/j.metabol.2021.154738 · Cited by 35
Liver Brain Interactions: Focus on FGF21 a Systematic Review
Prida, E., Álvarez-Delgado, S., Pérez-Lois, R., Soto-Tielas, M., Estany‐Gestal, A., Fernø, J., Seoane, L. M., Quiñones, M., & Al–Massadi, O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113318 · Cited by 40
“Importantly, high levels of FGF21 have been associated with different metabolic diseases, such as obesity [47], T2DM [48], non-alcoholic steatohepatitis (NASH) [49], cardiometabolic disorders [50], and congenital or acquired lipodystrophy [51,52].”
Background
Correlation of fibroblast growth factor 21 serum levels with metabolic parameters in Japanese subjects
Jin, Q., Bando, Y., Miyawaki, K., Shikama, Y., Kosugi, C., Aki, N., Funaki, M., & Noji, S. (2014) · The Journal of Medical Investigation · doi:10.2152/jmi.61.28 · Cited by 37
“Serum FGF21 levels are also increased in patients with type 2 diabetes, obesity (9-11) and Cushing’s syndrome (12).”
Fibroblast growth factor 21 correlates with weight loss after vertical sleeve gastrectomy in adolescents
Khan, F. H., Shaw, L., Zhang, W., Gonzalez, R. M. S., Mowery, S., Oehrle, M., Zhao, X., Jenkins, T. M., Setchell, K. D. R., Inge, T. H., et al. (2016) · Obesity · doi:10.1002/oby.21658 · Cited by 37
“Individuals with obesity have been found to have higher FGF21 levels than lean controls (26) and 3 weeks of a very low calorie diet is associated with a further increase in FGF21 levels (27).”
Background
The Role and Potential Therapeutic Implications of the Fibroblast Growth Factors in Energy Balance and Type 2 Diabetes
Izaguirre, M., Gil, M. J., Monreal, I., Montecucco, F., Frühbeck, G., & Catalán, V. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0866-3 · Cited by 41
Leptin as a Potential Regulator of FGF21
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“According to previous studies, FGF-21 is expressed predominantly in the liver and to a lesser extent in fat (Kharitonenkov et al. 2005, Mraz et al. 2009, Nishimura et al. 2000).”
BackgroundMethodInfluential
Significant gender difference in serum levels of fibroblast growth factor 21 in Danish children and adolescents
Bisgaard, A., Sørensen, K., Johannsen, T. H., Helge, J. W., Andersson, A., & Juul, A. (2014) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2014-7 · Cited by 34
“In accordance with the lack of association between FGF21 and anthropometric and biochemical parameters associated with obesity, we found no correlation between FGF21 and the adipokines leptin and adiponectin [27,28].”
Background
The alterations of serum FGF-21 levels, metabolic and body composition in early breast cancer patients receiving adjuvant endocrine therapy
Akyol, M., Alacacıoğlu, A., Demir, L., Küçükzeybek, Y., Yıldız, Y., Gumus, Z., Kara, M., Salman, T., Varol, U., Taşkaynatan, H., et al. (2017) · Cancer Biomarkers · doi:10.3233/cbm-161507 · Cited by 34
“Mraz et al. reported that under insulin resistance, serum FGF-21 level rises [30], and Lenart-Lipi´nska et al. showed that, in patients with type 2 diabetes, serum FGF-21 is predictive of combined cardiovascular morbidity and mortalityat the 24 th month of follow-up [31].”
Association between Serum Fibroblast Growth Factor 21 and Coronary Artery Disease in Patients with Type 2 Diabetes
Kim, W. J., Kim, S. S., Lee, H. C., Song, S. H., Bae, M. J., Yi, Y., Jeon, Y. K., Kim, B. H., Kim, Y. K., & Kim, I. J. (2015) · Journal of Korean Medical Science · doi:10.3346/jkms.2015.30.5.586 · Cited by 33
“The high levels of serum FGF-21 levels were associated with adverse lipid profile, obesity, and metabolic syndrome in other human studies (4, 9, 10).”
Background
Plasma Concentrations of Fibroblast Growth Factors 21 and 19 in Patients with Cushing's Syndrome
Ďurovcová, V., Marek, J., Hána, V., Matoulek, M., Zikán, V., Haluzíková, D., Kaválková, P., Lacinová, Z., Kršek, M., & Haluzı́k, M. (2010) · Physiological Research · doi:10.33549/physiolres.931801 · Cited by 33
FGF21 deficiency is associated with childhood obesity, insulin resistance and hypoadiponectinaemia: The BCAMS Study
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Changes in Plasma Concentrations and mRNA Expression of Hepatokines Fetuin A, Fetuin B and FGF21 in Physiological Pregnancy and Gestational Diabetes Mellitus
Šimják, P., Cinkajzlová, A., Anderlová, K., Kloučková, J., Kratochvílová, H., Lacinová, Z., Kaválková, P., Krejčí, H., Mráz, M., Pařı́zek, A., et al. (2018) · Physiological Research · doi:10.33549/physiolres.934017 · Cited by 32
GCN2 and FGF21 are likely mediators of the protection from cancer, autoimmunity, obesity, and diabetes afforded by vegan diets
McCarty, M. F. (2014) · Medical Hypotheses · doi:10.1016/j.mehy.2014.06.014 · Cited by 32
“positively with atherosclerosis [102–107].”
Fibroblast Growth Factor 21 Stimulates Pancreatic Islet Autophagy via Inhibition of AMPK-mTOR Signaling
Cheng, S. T. W., Li, S. Y. T., & Leung, P. S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102517 · Cited by 31
“Circulating FGF21 levels have been previously reported to be elevated in T2DM animal models and in human patients [5,38,39].”
Background
FGF21 as a Therapeutic Reagent
Zhao, Y., Dunbar, J. D., & Kharitonenkov, A. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0887-1_14 · Cited by 30
The role of FGF21 in type 1 diabetes and its complications
Zhang, J., Weng, W., Wang, K., Lu, X., Cai, L., & Sun, J. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.25026 · Cited by 30
“They observed that FGF21 levels in lean patients did not change during hyperinsulinemic-euglycemic clamp test, whereas insulin-induced increases in FGF21 were found in obese patients [36].”
BackgroundResult
Berberine stimulates fibroblast growth factor 21 by modulating the molecular clock component brain and muscle Arnt-like 1 in brown adipose tissue
Hirai, T., Mitani, Y., Kurumisawa, K., Nomura, K., Wang, W., Nakashima, K., & Inoue, M. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.04.017 · Cited by 31
Association of plasma FGF21 levels with muscle mass and muscle strength in a national multicentre cohort study: Korean Frailty and Aging Cohort Study
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Loss of FGF21 in diabetic mouse during hepatocellular carcinogenetic transformation.
Zhang, Q., Yan, L., Liang, T., Lu, X., Liu, X., Zhang, C., Jiang, X. M., Martin, R. C. G., Cheng, M., & Cai, L. (2015) · Europe PMC (PubMed Central) · Cited by 29
Effects of increased physical activity and/or weight loss diet on serum myokine and adipokine levels in overweight adults with impaired glucose metabolism
Tok, Ö., Kı̇şı̇oğlu, S. V., Ersöz, H. Ö., Kahveci, B., & Göktaş, Z. (2021) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2021.107892 · Cited by 31
Reduction in serum fibroblast growth factor-21 after gastric bypass is related to changes in hepatic fat content
Fjeldborg, K., Pedersen, S. B., Møller, H. J., & Richelsen, B. (2017) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2017.03.033 · Cited by 28
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Hulejová, H., Cerezo, L. A., Kuklová, M., Pecha, O., VONDRÁČEK, T., Pavelká, K., Vencovský, J., Haluzı́k, M., & Šenolt, L. (2012) · Physiological Research · doi:10.33549/physiolres.932324 · Cited by 28
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Association between insulin resistance and impairment of FGF21 signal transduction in skeletal muscles
Jeon, J. Y., Choi, S., Ha, E. S., Kim, T. H., Jung, J. G., Han, S. J., Kim, H. J., Kim, D. J., KANG, Y. Y., & Lee, K. W. (2016) · Endocrine · doi:10.1007/s12020-015-0845-x · Cited by 26
Relationship of fibroblast growth factor 21 with subclinical atherosclerosis and cardiovascular events: Multi-Ethnic Study of Atherosclerosis
Ong, K. L., Campbell, S., Wu, B. J., McClelland, R. L., Kokkinos, J., Szklo, M., Polak, J. F., Allison, M., & Rye, K.-A. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.06.898 · Cited by 25
FGF21-FGFR4 signaling in cardiac myocytes promotes concentric cardiac hypertrophy in mouse models of diabetes
Yanucil, C., Kentrup, D., Li, X., Grabner, A., Schramm, K. J., Martinez, E. C., Li, J., Campos, I. D., Czaya, B. A., Heitman, K., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-11033-x · Cited by 25
“In patients with T2D and obesity, however, markedly elevated serum FGF21 levels have been observed (An et al., 2012; Chavez et al., 2009; Mraz et al., 2009; Zhang et al., 2008), prompting the hypothesis that obesity is a FGF21-resistant metabolic state (Planavila et al., 2015b).”
Serum fibroblast growth factor 21 in human obesity: regulation by insulin infusion and relationship with glucose and lipid oxidation
Strączkowski, M., Karczewska‐Kupczewska, M., Adamska, A., Otziomek, E., Kowalska, I., & Nikołajuk, A. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.10 · Cited by 25
Serum Fibroblast Growth Factor 21 Levels Are Inversely Associated with Growth Rates in Infancy
Verónica Mericq, G., Luca, F. D., Hernández, M. I., Peña, V., Rossel, K., García, M., Ávila, A., Cavada, G., & Íñiguez, G. (2014) · Hormone Research in Paediatrics · doi:10.1159/000367922 · Cited by 25
Endocrine Fibroblast Growth Factors in Relation to Stress Signaling
Shimizu, M., & Sato, R. (2022) · Cells · doi:10.3390/cells11030505 · Cited by 25
“FGF21 is predominantly expressed in the liver and weakly expressed in white and brown adipose tissue [16,44].”
Background
Use of FGF21 analogs for the treatment of metabolic disorders: a systematic review and meta-analysis
Carbonetti, M. P., Almeida‐Oliveira, F., & Majerowicz, D. (2023) · Archives of Endocrinology and Metabolism · doi:10.20945/2359-4292-2022-0493 · Cited by 24
Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer
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Circulating FGF21 levels are related to nutritional status and metabolic but not hormonal disturbances in polycystic ovary syndrome
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Aerobic exercise for eight weeks provides protective effects towards liver and cardiometabolic health and adipose tissue remodeling under metabolic stress for one week: A study in mice
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Endoplasmic reticulum stress induces up-regulation of hepatic β-Klotho expression through ATF4 signaling pathway
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Serum FGF21 and RBP4 levels in patients with chronic hepatitis C
Kukla, M., Berdowska, A., Stygar, D. M., Gabriel, A., Mazur, W., Łogiewa-Bazger, B., Sobala‐Szczygieł, B., Bułdak, R. J., Rokitka, M., Zajęcki, W., et al. (2012) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2012.694901 · Cited by 23
“Nevertheless, this observation seems to be very interesting because it contradicts earlier findings that showed increased FGF21 serum levels in IR states [15,17].”
BackgroundResult
Fibroblast growth factor-4 maintains cellular viability while enhancing osteogenic differentiation of stem cell spheroids in part by regulating RUNX2 and BGLAP expression
Son, J., Tae, J., Min, S. K., Ko, Y., & Park, J. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.8951 · Cited by 22
Exenatide treatment decreases fasting fibroblast growth factor 21 levels in patients with newly diagnosed type 2 diabetes mellitus
Hu, Y., Liu, J., Zhang, H., Xu, Y., Hong, T., & Wang, G. (2016) · Diabetes & Metabolism · doi:10.1016/j.diabet.2016.04.005 · Cited by 22
Increased Serum Level of FGF21 in Gestational Diabetes Mellitus
Bonakdaran, S. (2017) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2017.278 · Cited by 21
“Glucotoxicity impairs FGF21 actions in pancreatic islet cells (17).”
Background
Fibroblast growth factor 21 and its relation to metabolic parameters in women with polycystic ovary syndrome
Şahin, S. B., Ayaz, T., Cüre, M. C., Sezgin, H., Ural, Ü. M., Balık, G., & Şahin, F. K. (2014) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365513.2014.900821 · Cited by 21
The relationship between Fibroblast Growth Factor-21 and characteristic parameters related to energy balance in dairy cows
Xu, C., Xu, Q., Chen, Y., Yang, W., Xia, C., Yu, H., Zhu, K., Shen, T., & Zhang, Z. (2015) · BMC Veterinary Research · doi:10.1186/s12917-015-0585-4 · Cited by 20
“Dairy cows under a controlled-energy diet showed a significant increase in serum FGF-21 levels, which can be interpreted as a response to a low-energy diet [17].”
Background
Fibroblast growth factor 21: A new liver safeguard
Cariello, M., & Moschetta, A. (2014) · Hepatology · doi:10.1002/hep.27147 · Cited by 20
Emerging roles of fibroblast growth factor 21 in critical disease
Fang, Y., Li, Y., Yang, F., Wu, G., & Jiang, X. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1053997 · Cited by 20
“Similarly, FGF21 concentrations were increased in patients treated with the PPARα agonist, fenofibrate (25).”
Background
Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls
Zibar, K., Blaslov, K., Bulum, T., Čuča, J. K., & Duvnjak, L. S. (2014) · Endocrine · doi:10.1007/s12020-014-0413-9 · Cited by 19
“FGF-21 concentrations were found in patients with type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome [2–7].”
Background
FGF-21: promising biomarker for detecting ketosis in dairy cows
Xu, C., Xu, Q., Chen, Y., Yang, W., Xia, C., Yu, H., Zhu, K., Shen, T., & Zhang, Z. (2016) · Veterinary Research Communications · doi:10.1007/s11259-015-9650-5 · Cited by 19
Impact of FGF21 on glycemic control
Strowski, M. Z. (2017) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2017-0001 · Cited by 20
Therapeutic applications of conditioned medium from adipose tissue
Dai, M., Zhang, Y., Yu, M., & Tian, W. (2016) · Cell Proliferation · doi:10.1111/cpr.12281 · Cited by 19
Laparoscopic gastric plication and its effect on saccharide and lipid metabolism: a 12-month prospective study.
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“In humans, increased FGF21 levels are associated with obesity in both children [29] and adults [30], indicating a connection between FGF21 and body fat mass.”
Background
Fibroblast growth factor 21 reverses high‐fat diet‐induced impairment of vascular function via the anti‐oxidative pathway in ApoE knockout mice
Huang, W., Chen, C., Lin, T., Kuo, C., Huang, H., Huang, P., & Lin, S. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17273 · Cited by 18
Effects of EPA and lipoic acid supplementation on circulating FGF21 and the fatty acid profile in overweight/obese women following a hypocaloric diet
Escoté, X., Félix‐Soriano, E., Gayoso, L., Huerta, A. E., Alvarado, M. A., Ansorena, D., Astiasarán, I., Martínez, J. A., & Moreno-Aliaga, M. J. (2018) · Food & Function · doi:10.1039/c8fo00355f · Cited by 17
Fibroblast growth factor 21 in dairy cows: current knowledge and potential relevance
Eder, K., Geßner, D. K., & Ringseis, R. (2021) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-021-00621-y · Cited by 18
Oral administration of a new HRI activator as a new strategy to improve high‐fat‐diet‐induced glucose intolerance, hepatic steatosis, and hypertriglyceridaemia through FGF21
Zarei, M., Pujol, E., Quesada‐López, T., Villarroya, F., Barroso, E., Vázquez, S., Pizarro‐Delgado, J., Palomer, X., & Vázquez‐Carrera, M. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14678 · Cited by 17
“, 2008) and humans (Chavez et al., 2009; Chen et al., 2008; Mraz et al., 2009), and especially in type 2 diabetes mellitus (T2DM; Badman, Kennedy, Adams, Pissios, & Maratos‐Flier, 2009; Zhang et al.”
Background
Activated brown adipose tissue and its relationship to adiposity and metabolic markers: an exploratory study
Soundarrajan, M., Deng, J., Kwasny, M., Rubert, N. C., Nelson, P. C., Abou-el-Seoud, D., Landsberg, L., & Neff, L. M. (2020) · Adipocyte · doi:10.1080/21623945.2020.1724740 · Cited by 20
Whey protein isolate inhibits hepatic FGF21 production, which precedes weight gain, hyperinsulinemia and hyperglycemia in mice fed a high-fat diet
Nonogaki, K., & Kaji, T. (2020) · Scientific Reports · doi:10.1038/s41598-020-72975-8 · Cited by 16
Novel Sandwich Immunoassays for The Measurement of Total and Active Fgf21
Umberger, T. S., Sloan, J. H., Chen, J., Cheng, C., Siegel, R. W., Qian, Y., Troutt, J. S., & Konrad, R. J. (2014) · Bioanalysis · doi:10.4155/bio.14.241 · Cited by 16
The Effect of FGF21 and Its Genetic Variants on Food and Drug Cravings, Adipokines and Metabolic Traits
Epperlein, S., Gebhardt, C., Rohde, K., Chakaroun, R., Patt, M., Schamarek, I., Kralisch, S., Heiker, J. T., Scholz, M. R., Stümvoll, M., et al. (2021) · Biomedicines · doi:10.3390/biomedicines9040345 · Cited by 16
“, after acute exercising [3], longterm fasting [4], very low caloric diet [5], excessive intake of carbohydrates [6], in the postprandial period [7], after alcohol consumption [8], and lipid infusion [9], in type 2 diabetes (T2D) [10], metabolic syndrome (MS) and obesity [11,12].”
Background
Integration of FGF21 Signaling and Metabolomics in High-Fat Diet-Induced Obesity
Zhou, Y., Li, C., Wang, X., Deng, P., He, W., Zheng, H. X., Zhao, L., & Gao, H. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00197 · Cited by 16
Hesperidin abrogates bisphenol A endocrine disruption through binding with fibroblast growth factor 21 (FGF-21), α-amylase and α-glucosidase: an in silico molecular study
Aja, P. M., Awoke, J. N., Agu, P. C., Adegboyega, A. E., Ezeh, E. M., Igwenyi, I. O., Orji, O. U., Ani, O. G., Ale, B. A., & Ibiam, U. A. (2022) · Journal of Genetic Engineering and Biotechnology · doi:10.1186/s43141-022-00370-z · Cited by 15
“FGF-21 is an indicator of metabolic syndrome and endocrine dysfunction [46] and BPA binding affinity to FGF-21 may be a novel mechanism of action of BPA in disrupting metabolic regulations leading to metabolic derangement in the body.”
Background
Serum fibroblast growth factor 21 in overweight and obese Thai children and adolescents: its relation to glucose metabolism and its change after glucose loading
Korwutthikulrangsri, M., Mahachoklertwattana, P., Chanprasertyothin, S., Pongratanakul, S., & Poomthavorn, P. (2015) · Clinical Endocrinology · doi:10.1111/cen.12808 · Cited by 15
Short-term dietary phosphate restriction up-regulates ileal fibroblast growth factor 15 gene expression in mice
Nakahashi, O., Yamamoto, H., Tanaka, S., Kozai, M., Takei, Y., Masuda, M., Kaneko, I., Taketani, Y., Iwano, M., Miyamoto, K., et al. (2014) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.13-109 · Cited by 15
Hepatic, adipocyte, enteric and pancreatic hormones: response to dietary macronutrient composition and relationship with metabolism
Hron, B. M., Ebbeling, C. B., Feldman, H. A., & Ludwig, D. S. (2017) · Nutrition & Metabolism · doi:10.1186/s12986-017-0198-y · Cited by 15
“However, FGF-21 levels are elevated in humans with obesity and type 2 diabetes mellitus [7], in association with markers of metabolic syndrome, which suggests a pattern of FGF-21 resistance [8] that may comprise a fourth component of the obesity-related resistance triad of insulin, leptin and sympathetic tone.”
Background
Adipose tissue contribution to plasma fibroblast growth factor 21 and fibroblast activation protein in obesity
van Baak, M. A., Vink, R., Roumans, N. J. T., Cheng, C., Adams, A. C., & Mariman, E. C. M. (2019) · International Journal of Obesity · doi:10.1038/s41366-019-0433-x · Cited by 15
Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids
Fiorenza, M., Checa, A., Sandsdal, R. M., Jensen, S. B. K., Juhl, C. R., Noer, M. H., Bogh, N. P., Lundgren, J. R., Janus, C., Stallknecht, B. M., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101629 · Cited by 14
The Level of FGF 21 as a New Risk Factor for the Occurrence of Cardiometabolic Disorders amongst the Psoriatic Patients
Kiluk, P., Baran, A. M., Kaminski, T. W., Maciaszek, M., & Flisiak, I. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8122206 · Cited by 15
Circulating levels of fibroblast growth factor 21 in gestational diabetes mellitus: a meta-analysis
Jia, J., Wei, W., Fan, Y., Liu, R., Shen, Y., Zhang, R., Yuan, G., & Zhou, H. (2020) · Endocrine Journal · doi:10.1507/endocrj.ej20-0481 · Cited by 14
“Women with GDM have an increased risk of obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD), along with their children [1-3].”
BackgroundInfluential
Cholesterol Metabolism Altered and FGF21 Levels High After Pediatric Liver Transplantation Despite Normal Serum Lipids
Kosola, S. K., Lampela, H., Gylling, H., Jalanko, H., Nissinen, M. J., Lauronen, J., Mäkisalo, H., Vaaralahti, K., Miettinen, T. A., Raivio, T., et al. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04147.x · Cited by 15
“Although dietary composition of fat and cholesterol may influence the noncholesterol sterol levels, the reported effect on FGF21 levels is controversial (20,33,34) in small study populations.”
BackgroundResult
Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis
Anuwatmatee, S., Allison, M., Shlipak, M. G., McClelland, R. L., Kramer, H., Tang, S., Hou, L., Rye, K., & Ong, K. L. (2018) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfy120 · Cited by 14
Effects of Moderate Chronic Food Restriction on the Development of Postprandial Dyslipidemia with Ageing
Fernández, A., Mazuecos, L., Pintado, C., Rubio, B., López, V., Solís, A. J. D., Rodríguez-Pérez, M., Andrés, A., & Gallardo, N. (2019) · Nutrients · doi:10.3390/nu11081865 · Cited by 13
“Additionally, we examined the expression of pivotal genes involved in fatty acid and lipoprotein uptake, lipogenesis, lipolysis, fat oxidation, and thermogenesis in these tissues, as well as the expression of the ChREBP target gene FGF21, because recent reports demonstrated that postprandial dyslipidemia and fatty liv…”
Background
Effects of Weight Loss on FGF-21 in Human Subjects: An Exploratory Study
Headland, M. L., Clifton, P. M., & Keogh, J. B. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16234877 · Cited by 13
“[23] showed an increase in FGF-21 levels after three weeks of a very low energy diet (resulting in moderate weight loss).”
Background
Attenuation of FGF21 signalling might aggravate the impairment of glucose homeostasis during the high sucrose diet induced transition from prediabetes to diabetes in WNIN/GR-Ob rats
Kondeti, S., Dinesh Yadav, D. M., Muralidhar, M. N., Prasad, S. M. V. K., Nemani, H., & Kalashikam, R. R. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111252 · Cited by 12
Placental fibroblast growth factor 21 is not altered in late-onset preeclampsia
Nitert, M. D., Scholz‐Romero, K., Kubala, M. H., McIntyre, D. H., Callaway, L. K., & Barrett, H. L. (2015) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-015-0006-3 · Cited by 13
“FGF21 is synthesized and secreted from the liver, adipose tissue, pancreatic β-cells, skeletal muscle, white blood cells and possibly cerebrospinal fluid [9-12].”
Background
Low Plasma Levels of Fibroblast Growth Factor-21 in Patients with Peripheral Artery Disease
Miyazaki, Y., Saita, E., Kishimoto, Y., Ibe, S., Seki, T., Miura, K., Sugihara, N., Ikegami, Y., Ohmori, R., Kondo, K. N., et al. (2018) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.41731 · Cited by 13
Fibroblast growth factor 21, adiposity, and macronutrient balance in a healthy, pregnant population with overweight and obesity
Sutton, E. F., Morrison, C. D., Stephens, J. M., & Redman, L. M. (2018) · Endocrine Research · doi:10.1080/07435800.2018.1473421 · Cited by 13
Association between Serum Fibroblast Growth Factor 21 Levels and Bone Mineral Density in Postmenopausal Women
Choi, H. S., Lee, H. A., Kim, S.-W., & Cho, E.-H. (2018) · Endocrinology and Metabolism · doi:10.3803/enm.2018.33.2.273 · Cited by 13
Effect of a 6-Week Carbohydrate-Reduced High-Protein Diet on Levels of FGF21 and GDF15 in People With Type 2 Diabetes
Richter, M. M., Thomsen, M. N., Skytte, M. J., Kjeldsen, S. A. S., Samkani, A., Frystyk, J., Magkos, F., Holst, J. J., Madsbad, S., Krarup, T., et al. (2024) · Journal of the Endocrine Society · doi:10.1210/jendso/bvae008 · Cited by 13
“Previous reports have been contradictory, with studies reporting increased or decreased levels of FGF21 following weight loss [48-50].”
Result
White adipose tissue in type 2 diabetes and the effect of antidiabetic drugs
Zhao, Y., & Yue, R. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01678-9 · Cited by 13
“FGF21 is a member of the FGF superfamily, and the expression of FGF21 mRNA in human SAT is positively associated with circulating levels of FGF21 [147].”
Association of FGF19, FGF21 and FGF23 with carbohydrate metabolism parameters and insulin resistance in patients with chronic kidney disease
Marchelek‐Myśliwiec, M., Dziedziejko, V., Dołęgowska, K., Pawlik, A., Safranow, K., Stępniewska, J., Wiśniewska, M., Małyszko, J., & Ciechanowski, K. (2020) · Journal of Applied Biomedicine · doi:10.32725/jab.2020.005 · Cited by 12
“Previous studies have reported increased FGF21 levels in patients with diabetes, obesity, arteriosclerosis and CKD (Mraz et al., 2009).”
Background
Circulating Fibroblast Growth Factor-21 and Risk of Metachronous Colorectal Adenoma
Florea, A., Harris, R. B., Klimentidis, Y. C., Kohler, L. N., Jurutka, P. W., & Jacobs, E. T. (2020) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-020-00515-8 · Cited by 11
Total serum FGF-21 levels positively relate to visceral adiposity differently from its functional intact form
Crudele, L., García‐Irigoyen, O., Cariello, M., Piglionica, M., Scialpi, N., Florio, M., Piazzolla, G., Suppressa, P., Sabbà, C., Gadaleta, R. M., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1159127 · Cited by 12
“Intriguingly, a difference in mRNA expression level between patients with and without obesity was found in VAT, but not in Subcutaneous AT (SAT) (11).”
Background
Prognostic value of plasma fibroblast growth factor 21 among patients with acute ischemic stroke
Zheng, X., Zhu, Z., Guo, D., Zhong, C., Xu, T., Peng, Y., Wang, A., Peng, H. Y., Ju, Z., Geng, D., et al. (2020) · European Journal of Neurology · doi:10.1111/ene.14683 · Cited by 12
The potential role of plasma fibroblast growth factor 21 as a diagnostic biomarker for abdominal aortic aneurysm presence and development
Xie, T., Yin, L., Guo, D., Zhang, Z., Chen, Y., Liu, B., Wang, W., & Zheng, Y. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119346 · Cited by 12
Endocrine FGFs and their signaling in the brain: Relevance for energy homeostasis
Zangerolamo, L., Carvalho, M. U. W. B. D., Velloso, L. A., & Barbosa, H. C. L. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.176248 · Cited by 11
Parsing the Potential Neuroendocrine Actions of FGF21 in Primates
Gillum, M. P. (2018) · Endocrinology · doi:10.1210/en.2018-00208 · Cited by 9
The relationship of circulating fibroblast growth factor 21 levels with incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis
Hui, T. H., McClelland, R. L., Allison, M., Rodríguez, C. J., Kronmal, R. A., Heckbert, S. R., Michos, E. D., Barter, P. J., Rye, K.-A., & Ong, K. L. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.12.026 · Cited by 10
“In the previous reports, plasma FGF21 levels have been reported to be associated with CHD [24], carotid atherosclerosis [25], and different cardiovascular risk factors, such as obesity, metabolic syndrome, type 2 diabetes, hypertriglyceridemia, hyperinsulinemia, pericardial fat volume, hypertension, and renal function…”
Background
High baseline FGF21 levels are associated with poor glucose-lowering efficacy of exenatide in patients with type 2 diabetes
Yang, K., Wang, H., Wei, R., Xiao, W., Tian, Q., Wang, C., Yang, J., & Hong, T. (2021) · Acta Diabetologica · doi:10.1007/s00592-020-01660-z · Cited by 9
Evaluating whole-genome expression differences in idiopathic and diabetic adhesive capsulitis
Gordon, J. A., Farooqi, A. S., Rabut, E., Huffman, G. R., Schug, J., Kelly, J. D. A., & Dodge, G. R. (2021) · Journal of Shoulder and Elbow Surgery · doi:10.1016/j.jse.2021.06.016 · Cited by 10
Decrypting the Possible Mechanistic Role of Fenofibrate in Alzheimer's Disease and Type 2 Diabetes: The Truth and Mystery
Alsaleem, M. A., Al-Kuraishy, H. M., Al-Gareeb, A. I., Abdel‐Fattah, M. M., Alrouji, M., Al‐Harchan, N. A., Alruwaili, M., Papadakis, M., Alexiou, A. T., & Batiha, G. E. (2025) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.70378 · Cited by 9
Response of fibroblast growth factor 21 to meal intake and insulin infusion in patients on maintenance haemodialysis
Reinhard, M., Frystyk, J., Jespersen, B., Randers, E., Bibby, B. M., & Ivarsen, P. (2015) · Clinical Endocrinology · doi:10.1111/cen.12737 · Cited by 9
Increased Fibroblast Growth Factor 21 (FGF21) Concentration in Early Second Trimester Amniotic Fluid and Its Association with Fetal Growth
Vrachnis, N., Argyridis, S., Vrachnis, D. N., Antonakopoulos, N., Valsamakis, G., Iavazzo, C. R., Zygouris, D., Salakos, N., Rodolakis, A., Vlahos, N., et al. (2021) · Metabolites · doi:10.3390/metabo11090581 · Cited by 9
“A very low-calorie diet has also been shown to increase FGF21 concentrations [26].”
Background
The Diagnostic Role of FGF 21 in Endometrial Cancer and Other Pathologies of the Uterine Corpus
Jagodzińska, A., Chudecka-Glaz, A. M., Michalczyk, K., Pius‐Sadowska, E., Wieder-Huszla, S., Jurczak, A., & Machaliński, B. (2023) · Diagnostics · doi:10.3390/diagnostics13030399 · Cited by 9
Fibroblast Growth Factor 21 Is Elevated in HIV and Associated With Interleukin-6
Eckard, A. R., Hughes, H., Hagood, N. L., O’Riordan, M. A., Labbato, D. E., Kosco, J. C., Scott, S., & McComsey, G. A. (2020) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000002285 · Cited by 8
Treatment with dapagliflozin increases FGF-21 gene expression and reduces triglycerides content in myocardial tissue of genetically obese mice
Vincenzo, A. D., Crescenzi, M., Granzotto, M., Vecchiato, M., Fioretto, P., Vettor, R., & Rossato, M. (2024) · Journal of Endocrinological Investigation · doi:10.1007/s40618-023-02273-3 · Cited by 8
“However, these results are in contrast with the common observation of higher circulating levels of FGF-21 in humans with obesity and T2DM [40], a counterintuitive condition defined as FGF-21 resistance, in which the chronic stimulation of the FGF-21 signaling leads to an inadequate response in…”
Serum Levels of Fibroblast Growth Factor 21 in Type 2 Diabetic Patient
Panahi, Y. (2016) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2016.257 · Cited by 8
“, FGF21 serum levels were significantly higher in patients with comorbid obesity and type 2 diabetes compared with the control group (11).”
Background

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
DOI: 10.1111/j.1365-2265.2008.03502.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Clinical Endocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › 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

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Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity

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