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

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. 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. 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). 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.