Obesity is caused by a combination of metabolic defect and long term imbalance between energy intake and energy expenditure. Leptin plays an important role in the regulation of food intake, and therefore it is of great interest to nutritional scientists studying obesity. Leptin is a polypeptide hormone that is expressed primarily in white adipose tissue and has structural similarities to cytokine hormones. The amount of leptin released from white adipose tissue is proportional to the energy reserves in that tissue. Therefore, as the amount of white adipose tissue accumulates due to energy imbalance, plasma levels of leptin rise. Leptin acts on receptors in the hypothalamus where it causes a decrease in the intake of food. Receptors for leptin are present in a number of other tissues which suggest it may have more than one function, probably involving reproductive behaviour.
Leptin is released from white adipose tissue in pulses with peak circulation in the morning and nadir in the afternoon. This pulsatile release is similar to many other hormones which demonstrate varying plasma levels based on circadian rhythms. The pattern of release of leptin from obese and non-obese individuals is known to be similar but obese individual produce higher plasma concentrations of leptin because they have larger energy reserves. When circulating leptin binds to receptors in the hypothalamus it cause two effects. Firstly, it causes the inhibition of orexigenic peptides, (e.g. neuropeptide Y, agouti related peptide), which act to increase food intake and decrease energy expenditure. Secondly, it causes the release of anorexigenic peptides (e.g. proopiomelanocortin and corticotropin-releasing hormone), which act to decrease food intake and increase energy expenditure.
The most likely scenario therefore, is that leptin is a feedback signal to the brain to convey information about the body’s energy stores to allow proper metabolic regulation of body fat. In addition, leptin in some way regulates the hypathalamo-pituitary-gonadal axis and reproductive behaviour, possibly increasing sexual behaviour in response to adequate energy reserves. Leptin levels are known to decrease rapidly in response to fasting, resulting in increased eating and decreased energy expenditure. Fasting is also known to decrease plasma testosterone levels in men and interfere with the female reproductive cycle. However, it is not clear why the high levels of leptin in obese individuals do not decrease food intake and increase energy expenditure. The most likely explanation is that the receptors for leptin become defective which results in an insensitivity to the hormone and a failure of adipose regulation.
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