FGF21 Levels in Pheochromocytoma/Functional Paraganglioma

. 2019 Apr 05 ; 11 (4) : . [epub] 20190405

Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid30959789

Grantová podpora
AZV 16-30345A Ministerstvo Zdravotnictví Ceské Republiky

Fibroblast growth factor 21 (FGF21) is a hepatokine with beneficial effects on metabolism. Our aim was to evaluate the relationship between the serum FGF21, and energy and glucose metabolism in 40 patients with pheochromocytoma/functional paraganglioma (PPGL), in comparison with 21 obese patients and 26 lean healthy controls. 27 patients with PPGL were examined one year after tumor removal. Basic anthropometric and biochemical measurements were done. Energy metabolism was measured by indirect calorimetry (Vmax-Encore 29N). FGF21 was measured by ELISA. FGF21 was higher in PPGL than in controls (174.2 (283) pg/mL vs. 107.9 (116) pg/mL; p < 0.001) and comparable with obese (174.2 (283) pg/mL vs. 160.4 (180); p = NS). After tumor removal, FGF21 decreased (176.4 (284) pg/mL vs. 131.3 (225) pg/mL; p < 0.001). Higher levels of FGF21 were expressed, particularly in patients with diabetes. FGF21 positively correlated in PPGL with age (p = 0.005), BMI (p = 0.028), glycemia (p = 0.002), and glycated hemoglobin (p = 0.014). In conclusion, long-term catecholamine overproduction in PPGL leads to the elevation in serum FGF21, especially in patients with secondary diabetes. FGF21 levels were comparable between obese and PPGL patients, despite different anthropometric indices. We did not find a relationship between FGF21 and hypermetabolism in PPGL. Tumor removal led to the normalization of FGF21 and the other metabolic abnormalities.

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Staiger H., Keuper M., Berti L., Hrabe de Angelis M., Haring H.U. Fibroblast Growth Factor 21-Metabolic Role in Mice and Men. Endocr. Rev. 2017;38:468–488. doi: 10.1210/er.2017-00016. PubMed DOI

BonDurant L.D., Potthoff M.J. Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis. Annu. Rev. Nutr. 2018;38:173–196. doi: 10.1146/annurev-nutr-071816-064800. PubMed DOI PMC

Domouzoglou E.M., Maratos-Flier E. Fibroblast growth factor 21 is a metabolic regulator that plays a role in the adaptation to ketosis. Am. J. Clin. Nutr. 2011;93:901S–905S. doi: 10.3945/ajcn.110.001941. PubMed DOI PMC

Fisher F.M., Kleiner S., Douris N., Fox E.C., Mepani R.J., Verdeguer F., Wu J., Kharitonenkov A., Flier J.S., Maratos-Flier E., et al. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev. 2012;26:271–281. doi: 10.1101/gad.177857.111. PubMed DOI PMC

Hondares E., Iglesias R., Giralt A., Gonzalez F.J., Giralt M., Mampel T., Villarroya F. Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J. Biol. Chem. 2011;286:12983–12990. doi: 10.1074/jbc.M110.215889. PubMed DOI PMC

Harms M., Seale P. Brown and beige fat: Development, function and therapeutic potential. Nat. Med. 2013;19:1252–1263. doi: 10.1038/nm.3361. PubMed DOI

Wang Q., Zhang M., Ning G., Gu W., Su T., Xu M., Li B., Wang W. Brown adipose tissue in humans is activated by elevated plasma catecholamines levels and is inversely related to central obesity. PLoS ONE. 2011;6:e21006. doi: 10.1371/journal.pone.0021006. PubMed DOI PMC

Hadi M., Chen C.C., Whatley M., Pacak K., Carrasquillo J.A. Brown fat imaging with (18)F-6-fluorodopamine PET/CT, (18)F-FDG PET/CT, and (123)I-MIBG SPECT: A study of patients being evaluated for pheochromocytoma. J. Nucl. Med. 2007;48:1077–1083. doi: 10.2967/jnumed.106.035915. PubMed DOI

Hondares E., Gallego-Escuredo J.M., Flachs P., Frontini A., Cereijo R., Goday A., Perugini J., Kopecky P., Giralt M., Cinti S., et al. Fibroblast growth factor-21 is expressed in neonatal and pheochromocytoma-induced adult human brown adipose tissue. Metabolism. 2014;63:312–317. doi: 10.1016/j.metabol.2013.11.014. PubMed DOI

BonDurant L.D., Ameka M., Naber M.C., Markan K.R., Idiga S.O., Acevedo M.R., Walsh S.A., Ornitz D.M., Potthoff M.J. FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms. Cell Metab. 2017;25:935–944. doi: 10.1016/j.cmet.2017.03.005. PubMed DOI PMC

Douris N., Stevanovic D.M., Fisher F.M., Cisu T.I., Chee M.J., Nguyen N.L., Zarebidaki E., Adams A.C., Kharitonenkov A., Flier J.S., et al. Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice. Endocrinology. 2015;156:2470–2481. doi: 10.1210/en.2014-2001. PubMed DOI PMC

Hsuchou H., Pan W., Kastin A.J. The fasting polypeptide FGF21 can enter brain from blood. Peptides. 2007;28:2382–2386. doi: 10.1016/j.peptides.2007.10.007. PubMed DOI PMC

Tan B.K., Hallschmid M., Adya R., Kern W., Lehnert H., Randeva H.S. Fibroblast growth factor 21 (FGF21) in human cerebrospinal fluid: Relationship with plasma FGF21 and body adiposity. Diabetes. 2011;60:2758–2762. doi: 10.2337/db11-0672. PubMed DOI PMC

Sarruf D.A., Thaler J.P., Morton G.J., German J., Fischer J.D., Ogimoto K., Schwartz M.W. Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats. Diabetes. 2010;59:1817–1824. doi: 10.2337/db09-1878. PubMed DOI PMC

Bookout A.L., de Groot M.H., Owen B.M., Lee S., Gautron L., Lawrence H.L., Ding X., Elmquist J.K., Takahashi J.S., Mangelsdorf D.J., et al. FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Nat. Med. 2013;19:1147–1152. doi: 10.1038/nm.3249. PubMed DOI PMC

Liang Q., Zhong L., Zhang J., Wang Y., Bornstein S.R., Triggle C.R., Ding H., Lam K.S., Xu A. FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting. Diabetes. 2014;63:4064–4075. doi: 10.2337/db14-0541. PubMed DOI

Martucci V.L., Pacak K. Pheochromocytoma and paraganglioma: Diagnosis, genetics, management, and treatment. Curr. Probl. Cancer. 2014;38:7–41. doi: 10.1016/j.currproblcancer.2014.01.001. PubMed DOI PMC

Xu J., Lloyd D.J., Hale C., Stanislaus S., Chen M., Sivits G., Vonderfecht S., Hecht R., Li Y.S., Lindberg R.A., et al. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes. 2009;58:250–259. doi: 10.2337/db08-0392. PubMed DOI PMC

Straczkowski M., Karczewska-Kupczewska M., Adamska A., Otziomek E., Kowalska I., Nikolajuk A. Serum fibroblast growth factor 21 in human obesity: Regulation by insulin infusion and relationship with glucose and lipid oxidation. Int. J. Obes. (Lond) 2013;37:1386–1390. doi: 10.1038/ijo.2013.10. PubMed DOI

Vienberg S.G., Brons C., Nilsson E., Astrup A., Vaag A., Andersen B. Impact of short-term high-fat feeding and insulin-stimulated FGF21 levels in subjects with low birth weight and controls. Eur. J. Endocrinol. 2012;167:49–57. doi: 10.1530/EJE-12-0039. PubMed DOI

Ďurovcová V., Marek J., Hána V., Matoulek M., Zikán V., Haluzíková D., Kaválková P., Lacinová Z., Kršek M., Haluzík M. Plasma concentrations of fibroblast growth factors 21 and 19 in patients with Cushing’s syndrome. Physiol. Res. 2010;59:415–422. PubMed

Petrák O., Haluzíkova D., Kaválková P., Štrauch B., Rosa J., Holaj R., Brabcová Vranková A., Michalský D., Haluzík M., Zelinka T., et al. Changes in energy metabolism in pheochromocytoma. J. Clin. Endocrinol. Metab. 2013;98:1651–1658. doi: 10.1210/jc.2012-3625. PubMed DOI

Zelinka T., Petrák O., Štrauch B., Holaj R., Kvasnička J., Mazoch J., Pacák K., Widimský J., Jr. Elevated inflammation markers in pheochromocytoma compared to other forms of hypertension. Neuroimmunomodulation. 2007;14:57–64. doi: 10.1159/000107289. PubMed DOI

Bosanská L., Petrák O., Zelinka T., Mráz M., Widimský J., Jr., Haluzík M. The effect of pheochromocytoma treatment on subclinical inflammation and endocrine function of adipose tissue. Physiol. Res. 2009;58:319–325. doi: 10.1016/S0953-6205(08)60153-3. PubMed DOI

Tsujimoto G., Manger W.M., Hoffman B.B. Desensitization of beta-adrenergic receptors by pheochromocytoma. Endocrinology. 1984;114:1272–1278. doi: 10.1210/endo-114-4-1272. PubMed DOI

Snavely M.D., Motulsky H.J., O’Connor D.T., Ziegler M.G., Insel P.A. Adrenergic receptors in human and experimental pheochromocytoma. Clin. Exp. Hypertens. A. 1982;4:829–848. doi: 10.3109/10641968209061616. PubMed DOI

Mráz M., Bartlová M., Lacinová Z., Michalský D., Kasalický M., Haluziková D., Matoulek M., Dostalová I., Humenanská V., Haluzík 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. 2009;71:369–375. doi: 10.1111/j.1365-2265.2008.03502.x. PubMed DOI

Zhang X., Yeung D.C., Karpisek M., Stejskal D., Zhou Z.G., Liu F., Wong R.L., Chow W.S., Tso A.W., Lam K.S., et al. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes. 2008;57:1246–1253. doi: 10.2337/db07-1476. PubMed DOI

Semba R.D., Sun K., Egan J.M., Crasto C., Carlson O.D., Ferrucci L. Relationship of serum fibroblast growth factor 21 with abnormal glucose metabolism and insulin resistance: The Baltimore Longitudinal Study of Aging. J. Clin. Endocrinol. Metab. 2012;97:1375–1382. doi: 10.1210/jc.2011-2823. PubMed DOI PMC

Lin Z., Gong Q., Wu C., Yu J., Lu T., Pan X., Lin S., Li X. Dynamic change of serum FGF21 levels in response to glucose challenge in human. J. Clin. Endocrinol. Metab. 2012;97:E1224–E1228. doi: 10.1210/jc.2012-1132. PubMed DOI

Vienberg S.G., Jacobsen S.H., Worm D., Hvolris L.E., Naver L., Almdal T., Hansen D.L., Wulff B.S., Clausen T.R., Madsbad S., et al. Increased glucose-stimulated FGF21 response to oral glucose in obese nondiabetic subjects after Roux-en-Y gastric bypass. Clin. Endocrinol. 2017;86:156–159. doi: 10.1111/cen.13241. PubMed DOI

Dushay J.R., Toschi E., Mitten E.K., Fisher F.M., Herman M.A., Maratos-Flier E. Fructose ingestion acutely stimulates circulating FGF21 levels in humans. Mol. Metab. 2015;4:51–57. doi: 10.1016/j.molmet.2014.09.008. PubMed DOI PMC

von Holstein-Rathlou S., BonDurant L.D., Peltekian L., Naber M.C., Yin T.C., Claflin K.E., Urizar A.I., Madsen A.N., Ratner C., Holst B., et al. FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver. Cell Metab. 2016;23:335–343. doi: 10.1016/j.cmet.2015.12.003. PubMed DOI PMC

Samms R.J., Lewis J.E., Norton L., Stephens F.B., Gaffney C.J., Butterfield T., Smith D.P., Cheng C.C., Perfield J.W., 2nd, Adams A.C., et al. FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans. J. Clin. Endocrinol. Metab. 2017;102:3806–3813. doi: 10.1210/jc.2017-01257. PubMed DOI PMC

Colwell J.A. Inhibition of insulin secretion by catecholamines in pheochromocytoma. Ann. Intern. Med. 1969;71:251–256. doi: 10.7326/0003-4819-71-2-251. PubMed DOI

Isles C.G., Johnson J.K. Phaeochromocytoma and diabetes mellitus: Further evidence that alpha 2 receptors inhibit insulin release in man. Clin. Endocrinol. 1983;18:37–41. doi: 10.1111/j.1365-2265.1983.tb03184.x. PubMed DOI

Cryer P.E. Adrenaline: A physiological metabolic regulatory hormone in humans? Int. J. Obes Relat Metab Disord. 1993;17(Suppl. 3):S43–S46; discussion S68. PubMed

Komada H., Hirota Y., So A., Nakamura T., Okuno Y., Fukuoka H., Iguchi G., Takahashi Y., Sakaguchi K., Ogawa W. Insulin Secretion and Insulin Sensitivity Before and After Surgical Treatment of Pheochromocytoma or Paraganglioma. J. Clin. Endocrinol. Metab. 2017;102:3400–3405. doi: 10.1210/jc.2017-00357. PubMed DOI

Fisher F.M., Chui P.C., Antonellis P.J., Bina H.A., Kharitonenkov A., Flier J.S., Maratos-Flier E. Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Diabetes. 2010;59:2781–2789. doi: 10.2337/db10-0193. PubMed DOI PMC

Hale C., Chen M.M., Stanislaus S., Chinookoswong N., Hager T., Wang M., Veniant M.M., Xu J. Lack of overt FGF21 resistance in two mouse models of obesity and insulin resistance. Endocrinology. 2012;153:69–80. doi: 10.1210/en.2010-1262. PubMed DOI

Markan K.R. Defining “FGF21 Resistance” during obesity: Controversy, criteria and unresolved questions. F1000Res. 2018;7:289. doi: 10.12688/f1000research.14117.1. PubMed DOI PMC

Markan K.R., Naber M.C., Ameka M.K., Anderegg M.D., Mangelsdorf D.J., Kliewer S.A., Mohammadi M., Potthoff M.J. Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding. Diabetes. 2014;63:4057–4063. doi: 10.2337/db14-0595. PubMed DOI PMC

Eisenhofer G., Lenders J.W., Goldstein D.S., Mannelli M., Csako G., Walther M.M., Brouwers F.M., Pacak K. Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines. Clin. Chem. 2005;51:735–744. doi: 10.1373/clinchem.2004.045484. PubMed DOI

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