These data demonstrate that LXRα S196A expressed in the bone marrow protects Ldlr−/− mice from diet-induced obesity when challenged by a western diet in part through a greater consumption of carbohydrates, which would reduce one of the substrates for lipid synthesis in adipocytes in LXRα S196A compared to WT mice. The gene discussed is NR1H3; the disease is obesity due to melanocortin 4 receptor deficiency.