Ablating Lepr from Agrp and/or Pomc neurons produces only mild obesity, however, though these manipulations impair glycemic control and other metabolic parameters (Balthasar et al. 2004; van de Wall et al. 2008; Berglund et al. 2012; Rupp et al. 2018). This evidence concerns the gene LEPR and obesity due to melanocortin 4 receptor deficiency.