Iron and obesity status-associated insulin resistance influence circulating fibroblast-growth factor-23 concentrations

PLoS One. 2013;8(3):e58961. doi: 10.1371/journal.pone.0058961. Epub 2013 Mar 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Ferritins / blood
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance*
  • Iron / metabolism*
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / metabolism*
  • Weight Loss

Substances

  • FGF23 protein, human
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Ferritins
  • Iron

Grants and funding

This work was supported by research grants from the Ministerio de Educación y Ciencia (SAF2005-02073), and Generalitat de Catalunya (2005SGR00947 and 2005SGR00467). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.