Increased Fibroblast Growth Factor 21 Serum Levels and Impaired Endothelial Function in Children With Obesity and Metabolic Disorder

Background: Obesity is linked to higher risk for endothelial dysfunction which is critical in the progression of cardiovascular disease. Obesity is constantly increasing in childhood. Early detection of metabolic disorders and cardiovascular risk is of utmost importance. Fibroblast growth factor 21 (FGF21) is known to influence metabolic pathways and is shown to be increased in the serum of obese adults. However, there are limited data regarding the potential role of FGF21 in metabolic and cardiovascular disorders in children.

Objective: Our aim was to investigate FGF21 serum levels and endothelial function in children with obesity and signs of metabolic disorder.

Methods: Seventy-eight children (8-16 years old) were classified as obese/overweight (n=41; 53% of total) and normal weight defined by age- and sex-specific body mass index percentiles. We defined metabolically unhealthy children as those with any classical feature of the metabolic syndrome (International Diabetes Federation criteria). Endothelial function was assessed by the brachial artery flow-mediated dilation (FMD) technique and normalized to the shear stimulus [i.e. peak%FMD normalized to shear rate (normalized FMD)]. The Mann-Whitney U test was used to investigate the differences between groups.

Results: In obese/overweight children, FGF21 serum levels were significantly increased [median 73.6 (interquartile range 41.6-127.8) vs. 30.4 (13.9-92.6) pg/ml, p=0.017] and normalized FMD was significantly lower [0.06 (0.04-0.09) vs. 0.09 (0.04-0.12), p=0.044] compared to normal BMI children. Metabolically unhealthy obese/overweight children (n=23; 29% of total) had significantly higher FGF21 serum levels [87.4 (49.1-185.5) vs. 29.3 (11.9-91.3) pg/ml, p=0.003] and a tendency for lower normalized FMD [0.06 (0.04-0.07) vs. 0.07 (0.04-0.12), p=0.082] compared to metabolically healthy normal weight children (n=32).

Conclusion: Obese/overweight and metabolically unhealthy obese/overweight children had increased FGF21 serum levels and impaired endothelial response to FMD. FGF21 may serve as a new biomarker that could be associated to obesity, metabolic disorders and endothelial dysfunction in childhood.