Methylation of a proximal region of the leptin promoter constitutes a significant determinant of leptin expression in human adult tissues [94] and variation in DNA methylation of the leptin promoter in animals models varies with the degree of obesity [95,96] and the epigenetic regulation of leptin signalling pathways can be manipulated by nutrients and food compounds as detailed recently [97]. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.