| Scientific Background: | The adipokine leptin is a hormone secreted predominantly by adipose tissue that signals through leptin receptors in the hypothalamus to decrease appetite and increase energy expenditure. Binding of leptin to the long-form of the leptin receptor in the hypothalamus reduces neuropeptide Y (NPY) and agouti-related protein (AgRP) activity, while stimulating anorexigenic pro-opiomelanocortin (POMC) neuron activity to reduce appetite. In peripheral tissues, leptin antagonizes insulin signaling, increases fatty acid oxidation, decreases insulin production in pancreatic beta cells, and promotes fertility. Its expression in adipocytes can be regulated in a paracrine fashion by other adipokines such as IL-6 (stimulation) and TNF-alpha (inhibition). Leptin deficient mice display severe insulin resistance, obesity, and decreased fertility, all of which are reversible by administration of exogenous leptin. In contrast, elevated circulating levels of leptin are associated with increased obesity, indicative of an acclimated state of leptin resistance which is not well understood. |
