Yonsei Med J.  2018 Mar;59(2):287-293. 10.3349/ymj.2018.59.2.287.

Serum Fibroblast Growth Factor 21 and New-Onset Metabolic Syndrome: KoGES-ARIRANG Study

Affiliations
  • 1Institute of Genomic Cohort, Yonsei University Wonju College of Medicine, Wonju, Korea. kimjang713@gmail.com
  • 2Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
  • 3Department of Thoracic and Cardiovascular Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea.
  • 4Department of Pharmacology, Yonsei University Wonju College of Medicine, Wonju, Korea.
  • 5Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea.
  • 6Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea.
  • 7Department of Anesthesiology and Pain Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. jtp999@yonsei.ac.kr
  • 8Department of Preventive Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

Abstract

PURPOSE
Fibroblast growth factor 21 (FGF21) is a crucial metabolic regulator, with multiple favorable effects on glucose homeostasis and lipid metabolism. Since serum FGF21 level has been implicated as a potential marker for the early identification of metabolic syndrome (MetS), we investigated the association between serum FGF21 level and the development of MetS in a population-based prospective study.
MATERIALS AND METHODS
We conducted a prospective study of 221 randomly sampled adults without MetS from a general population-based cohort study who were examined from 2005-2008 (baseline) and from 2008-2011 (follow-up). Baseline serum FGF21 levels were analyzed using enzyme-linked immunosorbent assay.
RESULTS
During the average 2.8-year follow-up period, 82 participants (36.6%) developed new-onset MetS. Serum FGF21 levels were significantly higher in patients with new-onset MetS than in those without MetS (209.56±226.80 vs. 110.09±81.10, p < 0.01). In multivariate adjusted models, the odds for MetS development were greater in patients with serum FGF21 levels in the highest quartile, compared to those in the lowest quartile (3.84, 95% confidence interval: 1.59-9.28).
CONCLUSION
Serum FGF21 level was an independent predictor for new-onset MetS in a population-based prospective study.

Keyword

Metabolic syndrome; fibroblast growth factor 21; biomarker; population-based prospective study

MeSH Terms

Biomarkers/blood
Female
Fibroblast Growth Factors/*blood
Humans
Male
Metabolic Syndrome/*blood
Middle Aged
Multivariate Analysis
Odds Ratio
Prospective Studies
Biomarkers
Fibroblast Growth Factors

Figure

  • Fig. 1 KoGES-ARIRANG study participant flow chart. KoGES-ARIRANG, Korean Genome and Epidemiology Study on the Atherosclerosis Risk of Rural Areas in the Korean General Population; MetS, metabolic syndrome.


Cited by  1 articles

Increased Serum Angiopoietin-Like 6 Ahead of Metabolic Syndrome in a Prospective Cohort Study
Jun Namkung, Joon Hyung Sohn, Jae Seung Chang, Sang-Wook Park, Jang-Young Kim, Sang-Baek Koh, In Deok Kong, Kyu-Sang Park
Diabetes Metab J. 2019;43(4):521-529.    doi: 10.4093/dmj.2018.0080.


Reference

1. Zhang X, Yeung DC, Karpisek M, Stejskal D, Zhou ZG, Liu F, et al. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes. 2008; 57:1246–1253. PMID: 18252893.
Article
2. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, et al. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005; 115:1627–1635. PMID: 15902306.
Article
3. Bobbert T, Schwarz F, Fischer-Rosinsky A, Pfeiffer AF, Möhlig M, Mai K, et al. Fibroblast growth factor 21 predicts the metabolic syndrome and type 2 diabetes in Caucasians. Diabetes Care. 2013; 36:145–149. PMID: 22933429.
Article
4. Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014; 4:1046–1061. PMID: 24893891.
Article
5. Domouzoglou EM, Naka KK, Vlahos AP, Papafaklis MI, Michalis LK, Tsatsoulis A, et al. Fibroblast growth factors in cardiovascular disease: the emerging role of FGF21. Am J Physiol Heart Circ Physiol. 2015; 309:H1029–H1038. PMID: 26232236.
Article
6. Bagheri L, Hami M, Mojahedi MJ, Ghorban Sabbagh M, Ayatollahi H. Association of metabolic syndrome with serum fibroblast growth factor 21 in kidney transplanted patients. J Renal Inj Prev. 2016; 5:79–84. PMID: 27471739.
Article
7. Zhou Z, Hu D, Chen J. Association between obesity indices and blood pressure or hypertension: which index is the best? Public Health Nutr. 2009; 12:1061–1071. PMID: 18778533.
Article
8. Matuszek B, Lenart-Lipin´ska M, Duma D, Solski J, Nowakowski A. Evaluation of concentrations of FGF-21 - a new adipocytokine in type 2 diabetes. Endokrynol Pol. 2010; 61:50–54. PMID: 20205104.
9. Ong KL, Rye KA, O'Connell R, Jenkins AJ, Brown C, Xu A, et al. Long-term fenofibrate therapy increases fibroblast growth factor 21 and retinol-binding protein 4 in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2012; 97:4701–4708. PMID: 23144467.
Article
10. Lim S, Shin H, Song JH, Kwak SH, Kang SM, Yoon JW, et al. Increasing prevalence of metabolic syndrome in Korea: the Korean National Health and Nutrition Examination Survey for 1998-2007. Diabetes Care. 2011; 34:1323–1328. PMID: 21505206.
11. Nestel P, Lyu R, Low LP, Sheu WH, Nitiyanant W, Saito I, et al. Metabolic syndrome: recent prevalence in East and Southeast Asian populations. Asia Pac J Clin Nutr. 2007; 16:362–367. PMID: 17468095.
12. Zhang M, Zeng L, Wang YJ, An ZM, Ying BW. Associations of fibroblast growth factor 21 gene 3′ untranslated region single-nucleotide polymorphisms with metabolic syndrome, obesity, and diabetes in a Han Chinese population. DNA Cell Biol. 2012; 31:547–552. PMID: 21988350.
Article
13. Lucero D, Miksztowicz V, Gualano G, Longo C, Landeira G, Álvarez E, et al. Nonalcoholic fatty liver disease associated with metabolic syndrome: influence of liver fibrosis stages on characteristics of very low-density lipoproteins. Clin Chim Acta. 2017; 473:1–8. PMID: 28802640.
Article
14. Ryu JY, Hong S, Kim CH, Lee S, Kim JH, Lee JT, et al. Prevalence of the metabolic syndrome among Korean workers by occupational group: fifth Korean National Health and Nutrition Examination Survey (KNHANES) 2010. Ann Occup Environ Med. 2013; 25:13. PMID: 24472422.
Article
15. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009; 120:1640–1645. PMID: 19805654.
16. Lee SY, Park HS, Kim DJ, Han JH, Kim SM, Cho GJ, et al. Appropriate waist circumference cutoff points for central obesity in Korean adults. Diabetes Res Clin Pract. 2007; 75:72–80. PMID: 16735075.
Article
17. Lundåsen T, Hunt MC, Nilsson LM, Sanyal S, Angelin B, Alexson SE, et al. PPARalpha is a key regulator of hepatic FGF21. Biochem Biophys Res Commun. 2007; 360:437–440. PMID: 17601491.
18. Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V, et al. Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell Metab. 2007; 5:415–425. PMID: 17550777.
19. 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. PMID: 17550778.
20. Moyers JS, Shiyanova TL, Mehrbod F, Dunbar JD, Noblitt TW, Otto KA, et al. Molecular determinants of FGF-21 activity-synergy and cross-talk with PPARgamma signaling. J Cell Physiol. 2007; 210:1–6. PMID: 17063460.
21. Wente W, Efanov AM, Brenner M, Kharitonenkov A, Köster A, Sandusky GE, et al. Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes. 2006; 55:2470–2478. PMID: 16936195.
22. Reitman ML. FGF21: a missing link in the biology of fasting. Cell Metab. 2007; 5:405–407. PMID: 17550773.
Article
23. Zhang F, Yu L, Lin X, Cheng P, He L, Li X, et al. Minireview: roles of fibroblast growth factors 19 and 21 in metabolic regulation and chronic diseases. Mol Endocrinol. 2015; 29:1400–1413. PMID: 26308386.
Article
24. Shen Y, Ma X, Zhou J, Pan X, Hao Y, Zhou M, et al. Additive relationship between serum fibroblast growth factor 21 level and coronary artery disease. Cardiovasc Diabetol. 2013; 12:124. PMID: 23981342.
Article
25. Lin Z, Wu Z, Yin X, Liu Y, Yan X, Lin S, et al. Serum levels of FGF-21 are increased in coronary heart disease patients and are independently associated with adverse lipid profile. PLoS One. 2010; 5:e15534. PMID: 21206918.
Article
26. Kim SH, Kim KH, Kim HK, Kim MJ, Back SH, Konishi M, et al. Fibroblast growth factor 21 participates in adaptation to endoplasmic reticulum stress and attenuates obesity-induced hepatic metabolic stress. Diabetologia. 2015; 58:809–818. PMID: 25537833.
Article
27. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004; 306:457–461. PMID: 15486293.
Article
28. Dushay J, Chui PC, Gopalakrishnan GS, Varela-Rey M, Crawley M, Fisher FM, et al. Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease. Gastroenterology. 2010; 139:456–463. PMID: 20451522.
Article
29. Muise ES, Azzolina B, Kuo DW, El-Sherbeini M, Tan Y, Yuan X, et al. Adipose fibroblast growth factor 21 is up-regulated by peroxisome proliferator-activated receptor gamma and altered metabolic states. Mol Pharmacol. 2008; 74:403–412. PMID: 18467542.
30. Fisher FM, Chui PC, Antonellis PJ, Bina HA, Kharitonenkov A, Flier JS, et al. Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Diabetes. 2010; 59:2781–2789. PMID: 20682689.
Article
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr