While prior studies suggest that sub-threshold liver fat may carry metabolic risk, the role of fibroblast growth factor-21 (FGF21)-a liver-derived hormone responsive to metabolic stress-has not been well characterised in this context.<h4>Objectives</h4>To examine the association between liver fat < 5% and metabolic markers in pubertal youth with obesity, with a focus on FGF21.<h4>Methods</h4>This secondary cross-sectional analysis included 58 pubertal adolescents with obesity (62% female; mean age 14.7 ± 1.7 years) and liver fat < 5% by MRI-proton density fat fraction (PDFF). The gene discussed is FGF21; the disease is obesity due to melanocortin 4 receptor deficiency.