Fibroblast growth factor-21 (FGF-21) is a novel regulator of metabolic homeostasis that improved diabetes compensation and dyslipidemia in diabetic mice and monkeys. However, little is known about its regulation in humans. Cushings syndrome (CS) is characterized by endogenous hypercortisolism and is often associated with numerous metabolic abnormalities. The objective of this study was to test the hypothesis that CS is associated with altered levels of FGF 21 that may in turn contribute to some metabolic disturbances and altered endocrine function of adipose tissue in these patients.
Biochemical, hormonal and anthropometric parameters, plasma levels of insulin, FGF-21, adipocyte fatty acid binding protein (AFABP) and adiponectin were measured by standard laboratory methods and commercial RIA (insulin) and ELISA kits (FGF-21, adiponectin, AFABP) in 16 patients with active CS, 20 patients with simple obesity (O) and 50 healthy controls (C).
BMI, insulin levels, HOMA index and AFABP were significantly higher in O and CS groups relative to C while serum adiponectin levels were decreased in both O and CS groups relative to C. Plasma FGF-21 levels were significantly higher in CS group relative to C (483.5±121.5 vs 197.3±36.6 pg/ml, P=0.002) but they did not significantly differ from O group (246.8±35 pg/ml). In a combined population of all three groups FGF-21 levels significantly positively correlated with waist circumference and percentage of truncal fat mass, blood pressure, triglyceride levels, HOMA index, insulin, glycated hemoglobin, leptin and AFABP levels and were inversely associated with plasma protein, albumin, HDL-cholesterol and free triiodothyronine levels.
We conclude that both obesity and CS are associated with paradoxically increased FGF-21 levels suggesting a possibility that resistance to FGF-21 rather than its deficiency may contribute to some metabolic disturbances in these patients.
Acknowledgements: Supported by IGA MHCR No. NR/9438-3 and MZOVFN2005 and approved by the local Ethical Committee.