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Abstract: TH-PO189

Effects of Induced Whole-Body Hypoxia on FGF23 in Obese Men

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Panwar, Bhupesh, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Peterson, Courtney M., University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Ravussin, Eric, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, United States
  • Gutierrez, Orlando M., The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background

Higher fibroblast growth factor 23 (FGF23) is associated with higher risk of heart disease and mortality in patients with chronic kidney disease (CKD). Recent evidence shows that Hypoxia Inducible Factor 1α (HIF-1α) is a direct transcriptional activator of FGF23. No study has directly tested the effect of induced hypoxia on FGF23 levels.

Methods

In a single-arm study design, 8 healthy obese men (BMI: 32.7 ± 3.7 kg/m2; age: 28 ± 3 years) were exposed to 10 consecutive nights of moderate hypoxia (15 ± 0.5% O2, simulating oxygen tension at 2400 m elevation) using hypoxic tents. Blood specimens and skeletal muscle and adipose biopsies were taken at baseline and after 10 days of hypoxic exposure. The primary outcomes were change in plasma intact FGF23 (iFGF23), c-terminal FGF23 (cFGF23) and FGF23 ratio (cFGF23:iFGF23). Paired t-test analysis was used to examine changes in log transformed values for iFGF23, cFGF23 and the FGF23 ratio. We also examined associations of muscle and adipose HIF-1α expression with FGF23.

Results

There were no statistically significant changes in either cFGF23 or iFGF23 after induced hypoxia. There was a statistically significant increase in the FGF23 ratio (1.05±0.11 to 1.08±0.11) post exposure to hypoxia (p=0.02)(Table). HIF-1α expression in muscle was significantly associated with iFGF23 (r=0.86,p<0.05) but not cFGF23 (r=0.11,P=0.45).

Conclusion

Exposure to hypoxia significantly increased the FGF23 ratio in obese men. In addition, muscle expression of HIF-1α was associated with iFGF23 plasma levels, suggesting that hypoxia influences FGF23 transcription and cleavage in humans.

Geometric mean Change (95%CI) in plasma FGF23 and arithmetic mean change (±SD) in FGF23 ratio with exposure to hypoxia.
 BaselinePost-Exposurep-value
cFGF2371.1 (26.4,190.9)75.3 (27.1,209.2)0.48
iFGF2358.9 (18.5,188.3)55.2 (16.0,189.8)0.38
FGF23 Ratio1.05 ± 0.111.08 ± 0.110.02