ACTN3 and obesity due to melanocortin 4 receptor deficiency: While the Actn3 KO 129X1/SvJ mice gained less weight compared to the wild-type (WT) mice when fed a high-fat diet (HFD) comprising 45% of calories from fat, the study found no significant contribution of the ACTN3 genotype alone to BMI or obesity in humans across six independent cohorts.