However, mice lacking PrRP in LEPRs producing neurons (PrRP-Cre, and Leprflox/flox mice) only develop mild obesity mainly due to lower energy expenditure (Dodd et al., 2014), which suggests that PrRP-producing neurons do not represent a major relay between leptin and the melanocortin signaling pathway. This evidence concerns the gene PRLH and obesity due to melanocortin 4 receptor deficiency.