In females, a significant genotype × fat level interaction was detected (<i>p</i> < 0.01), with AG carriers showing lower preference for high-fat sweet foods.<h4>Conclusions</h4>These findings indicate that the UCP1 A-3826G polymorphism may modulate preference for high-fat sweet foods in a sex-dependent manner, suggesting a link between thermogenic genetic variation and dietary fat preference relevant to obesity prevention. Here, UCP1 is linked to obesity due to melanocortin 4 receptor deficiency.