Nevertheless, sex differences in EE are the subject of intensive research and recently a study based on a novel 5-HT2CRCRE mouse line identified a specific population of pro-opiomelanocortin hypothalamic neurons expressing 5-hydroxytryptamine 2c receptors to drive a large sex difference in physical activity, energy expenditure and the development of obesity (Burke et al., 2016). Here, HTR2C is linked to obesity due to melanocortin 4 receptor deficiency.