A new study shows that C16 ceramide produced by LASS6 can accumulate in mitochondria and mitochondrial-related membranes and inhibit mitochondrial β-oxidation in the liver and brown adipose tissue, while LASS6-deficient mice can avoid obesity and glucose tolerance caused by high-fat foods [12]. Here, CERS6 is linked to obesity due to melanocortin 4 receptor deficiency.