LEPR and obesity due to melanocortin 4 receptor deficiency: It is interesting that the SF1-selective knockout of LepR (17) or cannabinoid receptor 1 (38) exacerbates the effects of high-fat diet, but the knock down of insulin receptors (39), SIRT1 nucleic acid deacetylase (40), or the FOXO1 transcription factor (41) has the opposing effect, and protects against diet-induced obesity.