Higher HOMA-IR (3rd/4th quantile) was linked to increased steatosis (β = 31.15, <i>p</i> = 0.032; β = 38.15, p = 0.023), whereas interactions of HOMA-IR × GDF-15 were inversely associated (β = -38.98, <i>p</i> = 0.008; β = -38.54, <i>p</i> = 0.019), suggesting a protective modulation.<h4>Conclusions</h4>GDF-15 appears to modulate hepatic steatosis and fibrosis in individuals with metabolic or lifestyle risk factors, supporting its potential as a therapeutic target and warranting further investigation of the neuro-metabolic-immunologic axis. The gene discussed is GDF15; the disease is Hepatic steatosis.