Journal of Endocrinology

A schematic of the leptin signalling pathway. Leptin is secreted by adipose tissue, circulates in the bloodstream to act on neurons in the arcuate nucleus of the hypothalamus which express the signalling form of the leptin receptor. SH2B1 is involved in leptin signalling. Activation of the leptin receptor leads to phosphorylation and activation of the transcription factor STAT3, which dimerises and translocates to the nucleus where it activates POMC gene transcription. POMC is post-translationally processed to yield the melanocortin peptides, which act on MC4R, located on the surface of neurons in the paraventricular nucleus of the hypothalamus. Activation of signalling through MC4R leads to a reduction in food intake. *Genes in which mutations are associated with severe early onset obesity.