Although it needs to be elucidated how cellular VLDL could be converted into C16:0 ceramides in macrophages, our data suggest that macrophage VLDLR could participate in alteration of certain sphingolipids via VLDL uptaking, which eventually leads to insulin resistance in obesity. The gene discussed is VLDLR; the disease is obesity due to melanocortin 4 receptor deficiency.