We confirm that young otherwise healthy ERαKO mice have an increased susceptibility to HFD-induced obesity compared to WT littermate controls (Heine et al., 2000; Ohlsson et al., 2000 #122) and further demonstrate that CL mitigates metabolic dysfunction caused by loss of ERα and HFD-induced obesity. This evidence concerns the gene ESR1 and obesity due to melanocortin 4 receptor deficiency.