Association between Serum Atypical Fibroblast Growth Factors 21 and 19 and Pediatric Nonalcoholic Fatty Liver Disease

PLoS One. 2013 Jun 26;8(6):e67160. doi: 10.1371/journal.pone.0067160. Print 2013.

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.

MeSH terms

  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Fibroblast Growth Factors / blood*
  • Gene Expression Regulation
  • Glucuronidase / metabolism
  • Humans
  • Klotho Proteins
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Male
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology

Substances

  • FGF19 protein, human
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Glucuronidase
  • Klotho Proteins

Grants and funding

V. Nobili was supported by a research grant from Bambino Gesù Children’s Hospital and Research Institute. A. Alisi was supported by a research grant (MFAG) from Associazione Italiana Ricerca sul Cancro (AIRC). The authors also thank Nicolò Valenti Onlus (Italy) for generous donation of Envision plate reader (Perkin Elmer, Italy). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.