Figure 1.
The Leptin/Melanocortin Pathway
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.
Figure 2.
Gene–Environment Interactions in Common Obesity
The complex interactions underlying polygenic obesity demonstrate that genetic, social, behavioral, and environmental factors are all capable of influencing the obese phenotype. The DNA strand should be interpreted as taking into account both genetic polymorphisms and the conformation of DNA structure (i.e., degree of methylation influenced by epigenetic events).
Figure 3.
Linkage Studies with Obesity-Related Phenotypes in Six Different Populations
All chromosomes but the Y chromosome have been found linked with an obesity-related phenotype (e.g., body mass index, fat mass, waist circumference, and blood pressure) in a least one population. Links for relatively few regions have been replicated in more than one population, as illustrated by colored boxes stacked horizontally. The figure was created using information in the most recent Human Obesity Gene Map update [6]. The American population comprises Caucasian, Hispanic, African, and Asian Americans.