Results: There were no genotype differences in HFD-induced obesity or systemic rescue effects of CL, yet ERβDBDKO females were more sensitive to CL-induced increases in energy expenditure and WAT UCP1 induction (GxT, p < 0.05), which coincided with greater WAT B3AR protein content among the KO (G, p < 0.05). This evidence concerns the gene UCP1 and obesity due to melanocortin 4 receptor deficiency.