Background

Fibroblast growth factor (FGF) 21 exerts its glycemic and insulin-sensitizing effects via adiponectin. Obesity is characterized by disturbances in FGF21-adiponectin axis. FGF21 concentration, regardless of the ethnicity/race, is positively associated with BMI; however, there is significant overlap in its serum levels among healthy, overweight and obese children. The aim of this study was to describe the relationship of FGF21-adiponectin ratio (FAR) to hepatic fat in children obese with or without NAFLD.

Methods

Sixty one (47% AA, 26% Hispanic, 26% White), obese (BMI≥95th%ile), pubertal (by Tanner staging), 10-17 years old children were recruited from a weight management clinic. Fasting blood sampling, % body fat estimation via bioimpedance analysis, and liver MRI for hepatic fat quantification was performed. FGF21 and adiponectin levels were measured via ELISA. NAFLD was defined as ≥5% liver fat. Subjects with and without NAFLD were compared.

Results

Compared to non-NAFLD subjects, 18 subjects (30%) with NAFLD had elevated ALT (42 ± 15 vs 29±11 IU/L, p=0.004), HOMA-IR (8.7 ± 4.5 vs 5.8 ± 3.8, p=0.022), and insulin (38 ± 20 vs 25 ± 15 mU/L, p=0.015), and lower HDL (39 ± 6 vs 45 ± 8 mg/dL, p=0.002). Mean age, BMIz, FGF21, adiponectin, and glucose did not statistically differ between groups (all 5 p> 0.108). Accounting for BMIz and ethnicity, a one-point increase in FAR was associated with a 1.6 percentage point increase in hepatic fat in Hispanics (p<0.001; n=16), and 0.17 percentage points increase in non-Hispanics (p=0.066, n=43) in both groups.

Conclusions

Higher FAR is associated with higher hepatic fat in obese, pubertal children, with a more pronounced relationship in Hispanics, regardless of baseline hepatic fat. FAR may be a useful surrogate marker to study the natural history of NAFLD and to monitor the success of its treatment.NIH 5P20GM109096 USDA/ARS 6026-51000-010-05S