Abstract
BackgroundFibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the pediatric population, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly investigated. We analyzed the role of FGF19, FGF21 and Klotho protein in children with normal body weight as well as in overweight and obese subjects and explored their associations with insulin resistance (IR) and metabolic syndrome (MS) and its components.MethodsThis was a cross-sectional study conducted in a group of hospitalized children and adolescents. Laboratory investigations included serum analysis of FGF19, FGF21, and Klotho with ELISA kits as well as the analysis of the lipid profile and ALT serum concentrations. Moreover, each subject underwent an oral glucose tolerance test (OGTT) with fasting insulinemia measurement to detect glucose tolerance abnormalities and calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Furthermore, the clinical analysis included blood pressure measurement, body fat percentage estimation and assessment of the prevalence of MS and its components.ResultsThe study was conducted with 174 children/adolescents aged 6–17 years with normal body weight (N = 48), obesity (N = 92) and overweight (N = 34). Klotho concentration was significantly higher in the obese children [median 168.6 pg/ml (90.2 to 375.9)]) than in the overweight [131.3 pg/ml (78.0 to 313.0)] and normal-body-weight subjects [116.6 pg/ml (38.5 to 163.9)] (p = 0.0334) and was also significantly higher in insulin-resistant children than in insulin-sensitive children [185.3 pg/ml (102.1 to 398.2) vs 132.6 pg/ml (63.9 to 275.6), p = 0.0283]. FGF21 was elevated in patients with MS compared to the FGF21 levels in other subjects [136.2 pg/ml (86.5 to 239.9) vs 82.6 pg/ml (41.8 to 152.4), p = 0.0286]. The multivariable model showed that FGF19 was an independent predictor of IR after adjusting for pubertal stage and BMI Z-score.ConclusionsKlotho levels were associated with body weight status in children and adolescents. Moreover, Klotho, FGF19 and FGF21 concentrations correlated with IR status and/or components of MS.
Highlights
Fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis
Klotho, FGF19 and FGF21 concentrations correlated with insulin resistance (IR) status and/or components of metabolic syndrome (MS)
The frequency of impaired glucose tolerance was similar across the groups, and neither being overweight [OR = 2.94] nor obese [OR = 2.70] was associated with significantly increased risk
Summary
Fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. Excessive body mass promotes insulin resistance (IR) in tissues, which increases the risk of type 2 diabetes, metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD). All these conditions contribute to future cardiovascular risk [3] and must be actively addressed. Particular interest has been given to the fibroblast growth factor subfamily 19, which includes fibroblast growth factor 19 (FGF19) and fibroblast growth factor 21 (FGF21) These hormones have been reported to regulate energy homeostasis in the prolonged response to nutritional status after insulin and glucagon action. FGF21, on the other hand, is released from the liver in response to starvation and exhibits glucagon-like properties: it promotes lipolysis, thermogenesis and gluconeogenesis [5,6,7]
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