Hypothalamic pro-opiomelanocortin neuron (POMC)–specific Atf4-KO mice are resistant to high-fat diet–induced obesity via enhanced autophagy-related 5-dependent autophagy and α-melanocyte–stimulating hormone production, suggesting that ATF4 in POMC neurons negatively regulates energy expenditure [54]. This evidence concerns the gene ATG5 and obesity due to melanocortin 4 receptor deficiency.