Alisi Anna, Ceccarelli Sara, Panera Nadia, Prono Federica, Petrini Stefania, De Stefanis Cristiano, Pezzullo Marco, Tozzi Alberto, Villani Alberto, Bedogni Giorgio, Nobili Valerio
Hepato-Metabolic Disease Unit and Liver Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
PLoS One. 2013 Jun 26;8(6):e67160. doi: 10.1371/journal.pone.0067160. Print 2013.
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.
非典型成纤维细胞生长因子（FGF）21和19通过共受体α-klotho的介导在能量代谢中发挥核心作用。关于FGF21和FGF19与人类非酒精性脂肪性肝病（NAFLD）的关联存在相互矛盾的研究结果。我们调查了血清FGF21、FGF19和肝脏共受体α-klotho与NAFLD儿童非酒精性脂肪性肝炎（NASH）和肝纤维化的关系。检测了84例经活检证实为NAFLD的儿童和23例对照（CTRL）的血清FGF21和FGF19。在7例对照、9例NASH患者（NASH+）和11例无NASH患者（NASH-）中检测了共受体α-klotho的肝脏表达。FGF21和FGF19呈现出从对照（FGF21中位数=196 pg/mL；FGF19中位数=201 pg/mL）到NASH-患者（FGF21=89 pg/mL；FGF19=81 pg/mL）再到NASH+患者（FGF21=54 pg/mL；FGF19=41 pg/mL）逐渐降低的趋势（所有比较p<0.001），并且与NAFLD儿童发生NASH和肝纤维化的可能性呈负相关。共受体α-klotho的肝脏表达与NASH呈负相关（R²=0.87，p<0.0001），与血清FGF21（R²=0.57，p<0.0001）和FGF19（R²=0.67，p<0.0001）呈正相关。总之，血清FGF19、FGF21和肝脏α-klotho表达与NAFLD儿童的肝损伤呈负相关，这些发现可能对理解NAFLD进展机制具有重要意义。
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