Participants without metabolic syndrome showed weaker leptin-MASLD associations (RRR 0.81, 95% CI 0.45–1.46, p = 0.485), while those with metabolic syndrome demonstrated enhanced susceptibility with a significant interaction effect (RRR 1.88, 95% CI 1.03–3.43, p = 0.041). Here, LEP is linked to metabolic syndrome.