Unraveling the Genetics of Human Obesity

The integration of signals from peripheral tissues in the hypothalamus is fundamental to the regulation of energy homeostasis. Distinct neuronal populations propagate the signaling of various molecules to control food intake and satiety. POMC neurons in the arcuate nucleus are activated by leptin and insulin and produce α-MSH, which then activates the MC4R receptor in the paraventricular nucleus, resulting in a satiety signal. The downstream roles of SIM1, BDNF, and TKRB are currently being explored. In contrast, a separate group of neurons expressing NPY and AGRP produce molecules that act as potent inhibitors of MC4R signaling. A dysfunction in these pathways will disrupt energy homeostasis. AGRP, agouti-related protein; α-MSH, alpha melanocyte stimulating hormone receptor; BDNF, brain-derived neurotropic factor; GHR, ghrelin receptor; ISR, insulin receptor; LepR, leptin receptor; NPY, neuropeptide Y; PC1 and 2, proconvertase 1 and 2; POMC, proopiomelanocortin; SIM1, single-minded homolog 1 (Drosophila); TRKB, tyrosine kinase receptor.

Publication

Unraveling the Genetics of Human Obesity. (2006) David M Mutch, et al. PLoS Genet. 2006 Dec;2(12):e188. Figure: F1. All organisms Homo sapiens Mus musculus Danio rerio

Disease mentions