Dose-response relationship between serum fibroblast growth factor 21 and liver fat content in non-alcoholic fatty liver disease.

BACKGROUND & AIM:Although serum fibroblast growth factor 21 (FGF21) levels are associated with liver fat content in non-alcoholic liver fat disease (NAFLD), the precise nature of the association remains undetermined. Therefore, this study aimed to explore the potential dose-response relationship between FGF21 and liver fat content in NAFLD. METHODS:For this exploratory study from a randomized trial, 220 NAFLD patients with central obesity were recruited via community-based screening and randomly assigned to either control, moderate or vigorous-moderate exercise groups for 12 months. After this exercise intervention, patients were followed-up for a further 12 months. Serum FGF21 levels were measured by ELISA. Intrahepatic triglyceride (IHTG) content was determined by proton magnetic resonance spectroscopy. RESULTS:Of the 220 patients, 149 (67.7%) were female; mean age was 53.9 ± 7.1 years and mean BMI was 28.0 ± 2.9 kg/m2 for all patients. Baseline IHGT increased gradually (P = 0.029 for trend) according to baseline serum FGF21 quartiles 1, 2, 3 and 4 (212.3, 358.9, 538.7 and 793.5 pg/mL, respectively). On grouping the distribution of serum FGF21 level changes into quartiles at month 12, the relative IHTG loss increased as serum FGF21 levels were reduced (P = 0.004 for trend). A similar trend was observed at month 24 (P = 0.006 for trend). Multivariate linear regression analysis revealed that changes in serum FGF21 levels were independently associated with changes in IHTG at both month 12 [β (SE), 0.136 (0.118); P = 0.048] and month 24 [β (SE), 0.152 (0.139); P = 0.041]. Using restricted cubic spline regression, changes in serum FGF21 were strongly and positively associated with their corresponding relative IHTG loss at both month 12 and follow-up (Poverall = 0.017, Pnon-linear = 0.044 and Poverall = 0.020, Pnon-linear = 0.361, respectively, for dose-response). CONCLUSION:Serum FGF21 is strongly associated with liver fat content in a dose-response manner in centrally obese NAFLD patients. These findings support the use of serum FGF21 as a biomarker of liver fat content in NAFLD.