In summary, we show here that rescue of ATP10D function in mice on C57BL/6J background leads to reduced HFD induced obesity and IR, altered hepatic expression of lipid-metabolism associated genes, including reduced SCD1 expression and the resulting decreased SCD1 product to precursor ratios, and distinct changes in the plasma lipoprotein pattern. Here, ATP10D is linked to obesity due to melanocortin 4 receptor deficiency.