Figure 1. Homeostasis feedback loop. After a meal, the nutrients, carbohydrates and fat are absorbed by the digestive tract and are used by the cells of the body to maintain themselves and to support the activities of the organism. Excess nutrient energy is stored primarily as fat in the adipose tissue. Leptin is released into the bloodstream from the adipose cells in proportion to these fat stores. Blood leptin levels may also be modulated by insulin, whose levels rise after a meal. Leptin will bind to the leptin receptor in the hypothalamus. Certain hypothalamic cell clusters (nuclei) contain neurons that express several known orexigenic (appetite stimulating) and anorexigenic (appetite repressing) peptides. Leptin is able to turn on or activate anorexigenic peptides while also inactivating or downregulating orexigenic peptides. Upon leptin stimulation (through receptor binding), the anorexigenic peptide POMC is processed to a smaller peptide, -melanocyte stimulating hormone (-MSH). Binding of -MSH to the melanocortin 4 receptor (MC4R) in turn signals satiety.

Figure 2. Cartoon of known obesity pathways in the hypothalamic satiety center. Shown here are neurons located in the hypothalamic nuclei around the third ventricle and some of their axonal projections. Key molecules and the steps disturbed in the mouse obesity mutations are indicated. ob: leptin mutation; db: diabetes mutation; fat: Cpe^fat mutation; A^y: lethal yellow mutation; ARC: arcuate nucleus; PVN: paraventricular nucleus; LH: lateral hypothalamus; VMH: ventromedial hypothalamus; LEPR: leptin receptor; INSR: insulin receptor; NPY: neuropeptide Y; AGRP: agouti-related protein; POMC: proopiomelanocortin; CART: cocaine amphetamine regulated transcript; MSH: melanin-stimulating hormone; MC4R: melanocortin receptor 4; NPYR: neuropeptide Y receptor; DA: dopamine; MCH: melanin-concentrating hormone; OX: orexin.