title: Association between Serum Atypical Fibroblast Growth Factors 21 and 19 and Pediatric Nonalcoholic Fatty Liver Disease.
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 (R(2) = 0.87, p<0.0001) and directly associated with serum FGF21 (R(2) = 0.57, p<0.0001) and FGF19 (R(2) = 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.
authors.affiliation: Hepato-Metabolic Disease Unit and Liver Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
authors.forename: Sara
authors.initials: S
authors.lastname: Ceccarelli
authors.forename: Nadia
authors.initials: N
authors.lastname: Panera
authors.forename: Federica
authors.initials: F
authors.lastname: Prono
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrini
authors.forename: Cristiano
authors.initials: C
authors.lastname: De Stefanis
authors.forename: Marco
authors.initials: M
authors.lastname: Pezzullo
authors.forename: Alberto
authors.initials: A
authors.lastname: Tozzi
authors.forename: Alberto
authors.initials: A
authors.lastname: Villani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bedogni
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D000090265:Klotho Proteins; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications / Q000378:metabolism / Q000473:pathology
chemical_list: C117476:FGF19 protein, human; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D005966:Glucuronidase; D000090265:Klotho Proteins