MC4R and obesity due to melanocortin 4 receptor deficiency: Secreted from fat cells, leptin acts on the hypothalamus through the blood-brain barrier, and ultimately suppresses appetite by triggering multiple signaling cascades like NPY, MC4R, CNR1. In peripheral tissues, multiple hormones or peptides affect lipid metabolism, such as leptin, neuropeptide Y, melanocortin, endocannabinoids, insulin, and norepinephrine, etc. Inhibition of lipolysis and stimulation of lipogenesis lead to hyperlipemia and obesity.