Fibroblast Growth Factor 19 Serum Levels: Relation to Renal Function and Metabolic Parameters

Abstract

Fibroblast growth factor 19 (FGF19) was recently introduced as a novel metabolic regulator reversing diabetes mellitus, hepatic steatosis, hyperlipidemia, and adiposity. In the current study, we determined circulating FGF19 levels in patients on chronic hemodialysis (CD) as compared to controls with a glomerular filtration rate (GFR) above 50 ml/min. FGF19 was measured by ELISA in control (n=60) and CD (n=60) patients and correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation, in both groups. Median serum FGF19 levels were 1.5-fold higher in CD patients (266.7 μg/l) as compared to subjects with a GFR above 50 ml/min (178.1 μg/l) (p=0.001). Furthermore, fasting glucose negatively and independently predicted circulating FGF19 in controls (p<0.05). Moreover, adiponectin was a positive and C-reactive protein was a negative independent predictor of FGF19 serum concentrations in CD patients. Taken together, we have demonstrated that circulating FGF19 levels are significantly increased in end-stage renal disease. Furthermore, FGF19 is associated with a beneficial metabolic profile in both control and CD patients.

Key words

FGF19 - hemodialysis - insulin resistance - obesity

References

• 1 Fasshauer M, Paschke R. Regulation of adipocytokines and insulin resistance.  Diabetologia. 2003;  46 1594-1603
• 2 Trujillo ME, Scherer PE. Adipose tissue-derived factors: impact on health and disease.  Endocr Rev. 2006;  27 762-778
• 3 Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, Sandusky GE, Hammond LJ, Moyers JS, Owens RA, Gromada J, Brozinick JT, Hawkins ED, Wroblewski VJ, Li DS, Mehrbod F, Jaskunas SR, Shanafelt AB. FGF-21 as a novel metabolic regulator.  J Clin Invest. 2005;  115 1627-1635
• 4 Kharitonenkov A, Wroblewski VJ, Koester A, Chen YF, Clutinger CK, Tigno XT, Hansen BC, Shanafelt AB, Etgen GJ. The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21.  Endocrinology. 2007;  148 774-781
• 5 Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states.  Cell Metab. 2007;  5 426-437
• 6 Fu L, John LM, Adams SH, Yu XX, Tomlinson E, Renz M, Williams PM, Soriano R, Corpuz R, Moffat B, Vandlen R, Simmons L, Foster J, Stephan JP, Tsai SP, Stewart TA. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes.  Endocrinology. 2004;  145 2594-2603
• 7 Tomlinson E, Fu L, John L, Hultgren B, Huang X, Renz M, Stephan JP, Tsai SP, Powell-Braxton L, French D, Stewart TA. Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity.  Endocrinology. 2002;  143 1741-1747
• 8 Bhatnagar S, Damron HA, Hillgartner FB. Fibroblast growth factor-19, a novel factor that inhibits hepatic fatty acid synthesis.  J Biol Chem. 2009;  284 10023-10033
• 9 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. 2008;  57 1246-1253
• 10 Chavez AO, Molina-Carrion M, Abdul-Ghani MA, Folli F, DeFronzo RA, Tripathy D. Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance.  Diabetes Care. 2009;  32 1542-1546
• 11 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;  32 126-128
• 12 Ziegelmeier M, Bachmann A, Seeger J, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine RBP-4 in relation to renal function.  Diabetes Care. 2007;  30 2588-2592
• 13 Seeger J, Ziegelmeier M, Bachmann A, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Serum Levels Of The Adipokine Vaspin in Relation to Metabolic And Renal Parameters.  J Clin Endocrinol Metab. 2008;  93 247-251
• 14 Ziegelmeier M, Bachmann A, Seeger J, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Adipokines influencing metabolic and cardiovascular disease are differentially regulated in maintenance hemodialysis.  Metabolism. 2008;  57 1414-1421
• 15 Sommer G, Ziegelmeier M, Bachmann A, Kralisch S, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M. Serum levels of adipocyte fatty acid binding protein are increased in chronic haemodialysis.  Clin Endocrinol (Oxf). 2008;  69 901-905
• 16 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
• 17 Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease.  J Am Soc Nephrol. 2002;  13 134-141
• 18 Merabet E, Dagogo-Jack S, Coyne DW, Klein S, Santiago JV, Hmiel SP, Landt M. Increased plasma leptin concentration in end-stage renal disease.  J Clin Endocrinol Metab. 1997;  82 847-850
• 19 Stejskal D, Karpisek M, Hanulova Z, Stejskal P. Fibroblast growth factor-19: development, analytical characterization and clinical evaluation of a new ELISA test.  Scand J Clin Lab Invest. 2008;  68 501-507

1 These authors contributed equally to this work.

Correspondence