title: Iron and obesity status-associated insulin resistance influence circulating fibroblast-growth factor-23 concentrations.
abstract: Fibroblast growth factor 23 (FGF-23) is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD). Circulating intact FGF-23 (iFGF-23) and C-terminal (CtFGF-23) concentrations (ELISA) were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1); and in association with fat mass and bone mineral density (DEXA) and atherosclerosis (intima media thickness, IMT) in 78 subjects (52 women) with a wide range of adiposity (Cohort 2). Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine) contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, CIBERobn Fisiopatología de la Obesidad y Nutrición CB06/03/010, Girona, Spain. jmfreal@idibgi.org
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
authors.forename: Josep
authors.initials: J
authors.lastname: Puig
authors.forename: Marta
authors.initials: M
authors.lastname: Serrano
authors.forename: Mónica
authors.initials: M
authors.lastname: Sabater
authors.forename: Antoni
authors.initials: A
authors.lastname: Rubió
authors.forename: José María
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.forename: Marina
authors.initials: M
authors.lastname: Fontan
authors.forename: Roser
authors.initials: R
authors.lastname: Casamitjana
authors.forename: Gemma
authors.initials: G
authors.lastname: Xifra
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Ortega
authors.forename: Javier
authors.initials: J
authors.lastname: Salvador
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
mesh_terms: D000328:Adult; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D005293:Ferritins / Q000097:blood; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D015431:Weight Loss
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005293:Ferritins; D007501:Iron
references.citation: Trends Endocrinol Metab. 2009 Jul;20(5):230-6
references.pmid: 19546009
references.citation: Nat Genet. 2006 Nov;38(11):1310-5
references.pmid: 17033621
references.citation: Am J Physiol Endocrinol Metab. 2006 Jul;291(1):E38-49
references.pmid: 16449303
references.citation: Nephrol Dial Transplant. 2009 Sep;24(9):2792-6
references.pmid: 19395730
references.citation: J Clin Invest. 2003 Sep;112(5):683-92
references.pmid: 12952917
references.citation: N Engl J Med. 2008 Aug 7;359(6):584-92
references.pmid: 18687639
references.citation: Biochem Biophys Res Commun. 2000 Oct 22;277(2):494-8
references.pmid: 11032749
references.citation: Cerebrovasc Dis. 2007;23(1):75-80
references.pmid: 17108679
references.citation: Scand J Clin Lab Invest. 2012 Apr;72(2):108-13
references.pmid: 22133206
references.citation: Atherosclerosis. 2009 Aug;205(2):385-90
references.pmid: 19181315
references.citation: J Clin Endocrinol Metab. 2011 Nov;96(11):3541-9
references.pmid: 21880793
references.citation: J Clin Endocrinol Metab. 2005 Mar;90(3):1519-24
references.pmid: 15613425
references.citation: J Clin Invest. 1987 Mar;79(3):790-800
references.pmid: 3546379
references.citation: J Clin Endocrinol Metab. 2010 Oct;95(10):4720-8
references.pmid: 20631025
references.citation: World Health Organ Tech Rep Ser. 1994;843:1-129
references.pmid: 7941614
references.citation: Clin Endocrinol (Oxf). 2012 Oct;77(4):537-40
references.pmid: 22103239
references.citation: Am J Med Sci. 2009 Feb;337(2):116-22
references.pmid: 19214027
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):E1146-55
references.pmid: 22006328
references.citation: Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):219-27
references.pmid: 20966399
references.citation: Nephrol Dial Transplant. 2009 Oct;24(10):3125-31
references.pmid: 19429932
references.citation: Atherosclerosis. 2009 Dec;207(2):546-51
references.pmid: 19524924
references.citation: J Clin Endocrinol Metab. 2002 Nov;87(11):4957-60
references.pmid: 12414858
references.citation: Ann Clin Biochem. 2007 Sep;44(Pt 5):463-6
references.pmid: 17761032
references.citation: Int J Endocrinol. 2011;2011:707126
references.pmid: 22164160
references.citation: Circulation. 2009 May 19;119(19):2545-52
references.pmid: 19414634
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):407-12
references.pmid: 19966287
references.citation: Proc Natl Acad Sci U S A. 2001 May 22;98(11):6500-5
references.pmid: 11344269
references.citation: Ann Intern Med. 2010 May 18;152(10):640-8
references.pmid: 20479029
references.citation: N Engl J Med. 2003 Apr 24;348(17):1656-63
references.pmid: 12711740
references.citation: Clin J Am Soc Nephrol. 2011 Dec;6(12):2871-8
references.pmid: 22034506
references.citation: J Clin Endocrinol Metab. 2012 May;97(5):1655-62
references.pmid: 22362819
references.citation: Osteoporos Int. 2009 Jul;20(7):1167-73
references.pmid: 18974917
references.citation: J Bone Miner Res. 2010 Aug;25(8):1711-23
references.pmid: 20200981