Leptin - Function

Function

Leptin acts on receptors in the hypothalamus of the brain, where it inhibits appetite

1. counteracting the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus)
2. counteracting the effects of anandamide (another potent feeding stimulant that binds to the same receptors as THC)
3. promoting the synthesis of α-MSH, an appetite suppressant.

This appetite inhibition is long-term, in contrast to the rapid inhibition of eating by cholecystokinin (CCK) and the slower suppression of hunger between meals mediated by PYY3-36. The absence of leptin (or its receptor) leads to uncontrolled food intake and resulting obesity. Several studies have shown fasting or following a very-low-calorie diet (VLCD) lowers leptin levels. In the short-term, leptin might be an indicator of energy balance. This system is more sensitive to starvation than to overfeeding; leptin levels change more when food intake decreases than when it increases. The dynamics of leptin due to an acute change in energy balance may be related to appetite and eventually to food intake. Although this is a new hypothesis, some data already support it.

Controversy is ongoing regarding the regulation of leptin by melatonin during the night. One research group suggested increased levels of melatonin caused a downregulation of leptin. However, in 2004, Brazilian researchers found melatonin to increase leptin levels in the presence of insulin, therefore causing a decrease in appetite during sleeping.

Mice with type 1 diabetes treated with leptin alone or in conjunction with insulin did better (blood sugar did not fluctuate as much; cholesterol levels decreased; less body fat formed) than those treated with insulin alone, raising the prospect of a new treatment for diabetes.