Fibroblast Growth Factor 21 Human ELISA

Summary

The fibroblast growth factor family (FGFs) are a family of more than 20 small (17–26 kDa) secreted peptides. The initial characterisation of these proteins focused on their ability to stimulate fibroblast proliferation through FGF receptors (FGFRs). Members of FGFs family play important roles in defining and regulating the development and function of endocrine tissues as well as modulating various metabolic processes. A recently described member of FGFs family, FGF-21, also called Fibroblast growth factor 21 precursor and UNQ3115/PRO10196, has been characterised as a potent metabolic regulator. FGF-21 is preferentially expressed in liver and regulates glucose uptake in human fat cells. Moreover, therapeutic administration of FGF-21 decreased plasma glucose levels and triglycerides to near normal levels in multiple mouse models of type 2 diabetes. Short-term treatment of normal or db/db mice with FGF-21 lowered plasma levels of insulin and improved glucose clearance compared with vehicle after oral glucose tolerance testing. Constant infusion of FGF-21 for 8 weeks in db/db mice nearly normalized fed blood glucose levels and increased plasma insulin levels. When administrated daily for 6 weeks to diabetic rhesus monkeys, FGF-21 caused dramatic decline in fasting plasma glucose, fructosamine, triglicerides, insulin, and glucagon. FGF-21 administration also led to significant improvements in lipoprotein profiles, including lowering of low-density lipoprotein cholesterol and raising of high-density lipoprotein cholesterol as well as beneficial changes in the circulating levels of several cardiovascular risk factors. FGF-21, when overexpressed, protected animals from diet-induced obesity. These results define a functional role for FGF-21 in vivo and provide evidence that FGF-21 can lower glucose and triglyceride levels in diabetic animals. In contrast to several members of the FGF family which may induce therapeutically undesirable in vivo proliferation of various cell types, a recent study demonstrated that FGF-21 did not induce mitogenicity, hypoglycemia or weight gain at any dose tested in diabetic or healthy animals or when overexpressed in transgenic mice. Thus, FGF-21 appears to have considerable potential for the treatment of diabetes mellitus.

Areas of investigation: Lipid metabolism, Diabetes mellitus type 2, Metabolic syndrome

Features

• It is intended for research use only
• The total assay time is less than 3.5 hours
• The kit measures FGF-21 in serum, plasma (EDTA, citrate, heparin)
• Assay format – 96 wells
• Quality controls are human serum based
• Standard is recombinant protein based
• Components of kit are provided ready to use, concentrated, lyophilized or in liquid form

Research topic

Energy metabolism and body weight regulation

Find out more on biovendor.com

• Fibroblast growth factor 21 in BioVendor News
• Fibroblast growth factor-21 mouse/rat elisa (fgf-21) in BioVendor News

Assay format

Sandwich ELISA, Biotin-labelled antibody

Applications

Plasma-Citrate, Plasma-EDTA, Plasma-Heparin, Serum

Sample requirements

75 µl/well

Storage/Shipping

Store the complete kit at 2–8°C. Under this condition, the kit is stable until the expiration date (see the label on the box).

Calibration Curve

Calibration range

30 to 1920 pg/ml

Limit of detection

Limit of Detection (LOD) (defined as concentration of analyte giving absorbance higher than mean absorbance of blank plus three standard deviations of the absorbance of blank: Ablank + 3×SDblank) is calculated from the real FGF-21 values in wells and is 7 pg/ml.

Intra-assay (Within-Run, n=6)

CV = 3.6 %

Inter-assay (Run-to-Run, n=6)

CV = 3.8 %

Spiking Recovery

100.4 %

Dilution Linearity

104.1 %

Cross-Reactivity

References to this product

• Christodoulides C, Dyson P, Sprecher D, Tsintzas K, Karpe F. Circulating fibroblast growth factor 21 is induced by peroxisome proliferator-activated receptor agonists but not ketosis in man. J Clin Endocrinol Metab. 2009 Sep;94 (9):3594-601
• Cuevas-Ramos D, Almeda-Valdes P, Gomez-Perez FJ, Meza-Arana CE, Cruz-Bautista I, Arellano-Campos O, Navarrete-Lopez M, Aguilar-Salinas CA. Daily physical activity, fasting glucose, uric acid, and body mass index are independent factors associated with serum fibroblast growth factor 21 levels. Eur J Endocrinol. 2010 Sep;163 (3):469-77
• Dostalova I, Haluzikova D, Haluzik M. Fibroblast growth factor 21: a novel metabolic regulator with potential therapeutic properties in obesity/type 2 diabetes mellitus. Physiol Res. 2009;58 (1):1-7
• Dostalova I, Kavalkova P, Haluzikova D, Lacinova Z, Mraz M, Papezova H, Haluzik M. Plasma concentrations of fibroblast growth factors 19 and 21 in patients with anorexia nervosa. J Clin Endocrinol Metab. 2008 Jun 17;
• Fazeli PK, Misra M, Goldstein M, Miller KK, Klibanski A. Fibroblast growth factor-21 may mediate growth hormone resistance in anorexia nervosa. J Clin Endocrinol Metab. 2010 Jan;95 (1):369-74
• Fisher FM, Chui PC, Antonellis PJ, Bina HA, Kharitonenkov A, Flier JS, Maratos-Flier E. Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Diabetes. 2010 Nov;59 (11):2781-9
• Han SH, Choi SH, Cho BJ, Lee Y, Lim S, Park YJ, Moon MK, Lee HK, Kang SW, Han DS, Kim YB, Jang HC, Park KS. Serum fibroblast growth factor-21 concentration is associated with residual renal function and insulin resistance in end-stage renal disease patients receiving long-term peritoneal dialysis. Metabolism. 2010 Nov;59 (11):1656-62
• Hero M, Dunkel L, Vaaralahti K, Raivio T. Serum FGF21 in Boys with Idiopathic Short Stature: Relationship to Lipid Profile, Onset of Puberty and Growth*. Clin Endocrinol (Oxf). 2011 Feb 1;
• Hojman P, Pedersen M, Nielsen AR, Krogh-Madsen R, Yfanti C, Akerstrom T, Nielsen S, Pedersen BK. Fibroblast growth factor-21 is induced in human skeletal muscles by hyperinsulinemia. Diabetes. 2009 Dec;58 (12):2797-801
• Kotulak T, Drapalova J, Kopecky P, Lacinova Z, Kramar P, Riha H, Netuka I, Maly J, Housa D, Blaha J, Svacina S, Haluzik M. Increased circulating and epicardial adipose tissue mRNA expression of fibroblast growth factor-21 after cardiac surgery: possible role in postoperative inflammatory response and insulin resistance. Physiol Res. 2011 Nov 22;60 (5):757-67
• Li H, Bao Y, Xu A, Pan X, Lu J, Wu H, Lu H, Xiang K, Jia W. Serum Fibroblast Growth Factor 21 is Associated with Adverse Lipid Profiles and {gamma}-glutamyltransferase but not Insulin Sensitivity in Chinese Subjects. J Clin Endocrinol Metab. 2009 Mar 24;
• Li X, Fan X, Ren F, Zhang Y, Shen C, Ren G, Sun J, Zhang N, Wang W, Ning G, Yang J. Serum FGF21 levels are increased in newly diagnosed type 2 diabetes with nonalcoholic fatty liver disease and associated with hsCRP levels independently. Diabetes Res Clin Pract. 2011 Jul;93 (1):10-6
• Lin Z, Wu Z, Yin X, Liu Y, Yan X, Lin S, Xiao J, Wang X, Feng W, Li X. Serum levels of FGF-21 are increased in coronary heart disease patients and are independently associated with adverse lipid profile. PLoS One. 2010;5 (12):e15534
• Lin Z, Zhou Z, Liu Y, Gong Q, Yan X, Xiao J, Wang X, Lin S, Feng W, Li X. Circulating FGF21 levels are progressively increased from the early to end stages of chronic kidney diseases and are associated with renal function in Chinese. PLoS One. 2011;6 (4):e18398
• Mashili FL, Austin RL, Deshmukh AS, Fritz T, Caidahl K, Bergdahl K, Zierath JR, Chibalin AV, Moller DE, Kharitonenkov A, Krook A. Direct effects of FGF21 on glucose uptake in human skeletal muscle: implications for type 2 diabetes and obesity. Diabetes Metab Res Rev. 2011 Mar;27 (3):286-97
• Matuszek B, Lenart-Lipinska M, Duma D, Solski J, Nowakowski A. Evaluation of concentrations of FGF-21 - a new adipocytokine in type 2 diabetes. Endokrynol Pol. 2010 Jan-Feb;61 (1):50-4
• Mraz M, Bartlova M, Lacinova Z, Haluzikova D, Humenanska V, Haluzik M. Serum concentrations of novel metabolic regulator FGF–21 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet and PPAR-α agonist treatment. Poster presented in ADA 2008;
• Mraz M, Bartlova M, Lacinova Z, Michalsky D, Kasalicky M, Haluzikova D, Matoulek M, Dostalova I, Humenanska V, Haluzik M. Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity. Clin Endocrinol (Oxf). 2009 Sep;71 (3):369-75
• Samson SL, Sathyanarayana P, Jogi M, Gonzalez EV, Gutierrez A, Krishnamurthy R, Muthupillai R, Chan L, Bajaj M. Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. Diabetologia. 2011 Sep 29;
• Sarruf DA, Thaler JP, Morton GJ, German J, Fischer JD, Ogimoto K, Schwartz MW. Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats. Diabetes. 2010 Jul;59 (7):1817-24
• Stein S, Bachmann A, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine FGF21 depend on renal function. Diabetes Care. 2009 Jan;32 (1):126-8
• Stein S, Stepan H, Kratzsch J, Verlohren M, Verlohren HJ, Drynda K, Lossner U, Bluher M, Stumvoll M, Fasshauer M. Serum fibroblast growth factor 21 levels in gestational diabetes mellitus in relation to insulin resistance and dyslipidemia. Metabolism. 2009 Aug 20;
• Suomalainen A, Elo JM, Pietilainen KH, Hakonen AH, Sevastianova K, Korpela M, Isohanni P, Marjavaara SK, Tyni T, Kiuru-Enari S, Pihko H, Darin N, Ounap K, Kluijtmans LA, Paetau A, Buzkova J, Bindoff LA, Annunen-Rasila J, Uusimaa J, Rissanen A, Yki-Jarvinen H, Hirano M, Tulinius M, Smeitink J, Tyynismaa H. FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study. Lancet Neurol. 2011 Sep;10 (9):806-18
• Zhang X, Yeung DC, Karpisek M, Stejskal D, Zhou ZG, Liu F, Wong RL, Chow WS, Tso AW, Lam KS, Xu A. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes . Feb 5 (2008)

References to summary

• Chen WW, Li L, Yang GY, Li K, Qi XY, Zhu W, Tang Y, Liu H, Boden G.: Circulating FGF-21 Levels in Normal Subjects and in Newly Diagnose Patients with Type 2 Diabetes Mellitus.Exp Clin Endocrinol Diabetes. 2008 Jan;116(1):65–8.
• Kharitonenkov A, Shanafelt AB.: Fibroblast growth factor-21 as a therapeutic agent for metabolic diseases.BioDrugs. 2008;22(1):37–44.
• Kharitonenkov A, Dunbar JD, Bina HA, Bright S, Moyers JS, Zhang C, Ding L, Micanovic R, Mehrbod SF, Knierman MD, Hale JE, Coskun T, Shanafelt AB.: FGF-21/FGF-21 receptor interaction and activation is determined by betaKlotho.J Cell Physiol. 2008 215(1):1–7.
• Suzuki M, Uehara Y, Motomura-Matsuzaka K, Oki J, Koyama Y, Kimura M, Asada M, Komi-Kuramochi A, Oka S, Imamura T.: {beta}Klotho is required for FGF21 signaling FGFR1c and FGFR3c.Mol Endocrinol. 2008
• Kharitonenkov A., Wroblewski V.J., Koester A., Chen Y-F., Clutinger C.K., Tigno X.T., Hansen B.C., Shanafelt A.B. and Etgen G.J.: The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21.Endocrinology 148(2):774–81(2007)
• Moore D.D.:Physiology. Sister act. Science 316(5830):1436–8 (2007)
• Ogawa Y., Kurosu H., Yamamoto M., Nandi A., Rosenblatt K.P., Goetz R., Eliseenkova A.V., Mohammadi M. and Kuro-o M.: BetaKlotho is required for metabolic activity of fibroblast growth factor 21.Proc Natl Acad Sci U S A. 104(18):7432–7 (2007)
• Wente W., Efanov A.M., Brenner M., Kharitonenkov A., Koster A., Sandusky G.E., Sewing S., Treinies I., Zitzer H. and Gromada J.: Fibroblast Growth Factor-21 Improves Pancreatic beta-cells Function and Survival by Activation of Extracellular Signal-Regulated Kinase 1/2 and Akt Signaling Pathway.Diabetes, Vol 55:2470–2478(2006)
• Kharitonenkov A., Shiyanova L.T., Koester A., Ford A.M., Micanovic R., Galbreath E.J.,Sandusky G.E., Hammond L.J., Moyers J.S., Owens R.A., Gromada J., Brozinick J.T., Hawkins E.D., Wroblewski V.J., Li D-S, Mehrbod F., Jaskunas S.R. and Shanafelt A.B.: FGF-21 as a novel metabolic regulator.J Clin Invest.115:1627–1635 (2005)

By research topic:

• Energy metabolism and body weight regulation

By molecule:

• Fibroblast Growth Factor 21

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