Accordingly, the decreased energy intake fully accounts for decreased weight gain in male NT-PGC-1α−/− mice, whereas the incomplete digestion and inefficient absorption of dietary fat, along with the decreased fatty acid uptake in adipose tissue, likely contribute to the greater resistance of NT-PGC-1α−/− female mice to HFD-induced obesity. Here, PPARGC1A is linked to obesity due to melanocortin 4 receptor deficiency.