Abstract
Atypical fibroblast growth factors (FGF) 21 and 19 play a central role in energy metabolism through the mediation of Klotho coreceptor. Contradictory findings are available about the association of FGF21 and FGF19 with nonalcoholic fatty liver disease (NAFLD) in humans. We investigated the association of serum FGF21, FGF19 and liver Klotho coreceptor with non-alcoholic steatohepatitis (NASH) and fibrosis in children with NAFLD. Serum FGF21 and FGF19 were measured in 84 children with biopsy-proven NAFLD and 23 controls (CTRL). The hepatic expression of Klotho coreceptor was measured in 7 CTRL, 9 patients with NASH (NASH+) and 11 patients without NASH (NASH−). FGF21 and FGF19 showed a tendency to decrease from CTRL (median FGF21 = 196 pg/mL; median FGF19 = 201 pg/mL) to NASH− (FGF21 = 89 pg/mL; FGF19 = 81 pg/mL) to NASH+ patients (FGF21 = 54 pg/mL; FGF19 = 41 pg/mL) (p<0.001 for all comparisons) and were inversely associated with the probability of NASH and fibrosis in children with NAFLD. The hepatic expression of Klotho coreceptor was inversely associated with NASH (R2 = 0.87, p<0.0001) and directly associated with serum FGF21 (R2 = 0.57, p<0.0001) and FGF19 (R2 = 0.67, p<0.0001). In conclusion, serum FGF19 and FGF21 and hepatic Klotho expression are inversely associated with hepatic damage in children with NAFLD and these findings may have important implications for understanding the mechanisms of NAFLD progression.
Highlights
The prevalence of non-alcoholic fatty liver disease (NAFLD), which is considered the hepatic manifestation of the metabolic syndrome (MS), is rapidly increasing worldwide [1]
This evidence suggests that FGF21 and its networked molecular environment is a supervisor of lipid accumulation in adipose tissue and other peripheral organs such as the liver [7]
The median levels of FGF21 and FGF19 were significantly lower in NAFLD patients with respect to controls (p,0.001, quantile regression)
Summary
The prevalence of non-alcoholic fatty liver disease (NAFLD), which is considered the hepatic manifestation of the metabolic syndrome (MS), is rapidly increasing worldwide [1]. Obesity and selected components of the MS are known risk factors for NALFD [3], the mechanisms by which these factors produce the large spectrum of disease typical of NAFLD are largely unknown [4,5]. In this respect, it is very interesting that fibroblast growth-factor (FGF21), an autophagy-regulated mitokine, has been shown to play a central role in the maintenance of glucose and lipid homeostasis [6]. This evidence suggests that FGF21 and its networked molecular environment is a supervisor of lipid accumulation in adipose tissue and other peripheral organs such as the liver [7]
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