Apart from obesity increasing insulin, IGF-1, leptin, IL-6, TNF-α and decreasing levels of adiponectin which activates the PI3K-AKT signalling pathway in CRC, high BMI inhibits methylation of PI3K-AKT signalling pathway genes, constitutively activating the pathway [143]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.