Leptin is a hormone produced primarily by your fat tissue. It plays a key role in controlling appetite and regulating the amount of energy you burn. In addition, leptin is instrumental in immune and reproductive function, and it participates in bone growth and tissue repair and remodeling. Leptin deficiency or a deficient response to leptin has been implicated as a cause of morbid obesity. Congenital leptin deficiency, which arises from defects in the gene that controls leptin production, represents an extremely rare form of leptin deficiency.
Genetics
Much of scientists' knowledge about leptin's actions has come from the study of obese mice that produce abnormally low amounts of leptin or that do not respond to the hormone due to defective cellular receptors. In 1994, researchers discovered that the gene which regulates leptin production in the human body is quite similar to that found in mice. Therefore, many of leptin's effects --- and the manifestations of leptin deficiency --- are similar in both species. A review of results was published in the "International Journal of Obesity" in November 2002.
Actions
Leptin's actions in the brain and other organs --- lungs, liver, heart, kidneys, gonads, adrenal glands and fat tissue, to name a few --- are mediated through leptin-specific receptors in these tissues. Although its actions are complex and incompletely understood, leptin suppresses appetite and decreases food consumption, improves energy consumption in muscles and other tissues and enhances fertility and gonadal development. Congenital leptin deficiency, by virtue of insufficient leptin production, is characterized by abnormalities in all of these functions.
Congenital Deficiency
Scientists at the Australian National University in Canberra report in the "International Journal of Obesity" article that untreated congenital leptin deficiency is manifested by morbid obesity, reproductive failure and early death. Diabetes is also a frequent finding in affected patients. Treatment with leptin effectively reverses many of these abnormalities: patients lose weight, their reproductive function improves, glucose metabolism is enhanced, and measurements of thyroid, adrenal and pituitary function all improve. These favorable responses to leptin administration indicate that the main defect in congenital leptin deficiency is a lack of leptin production, rather than problems with receptors.
Considerations
Leptin caught the attention of scientists and laypersons in the mid 1990s, as it seemed to be a good agent for treating obesity and its many complications. In the intervening years, research on animal and human models of leptin-deficient states has shed some light on leptin's actions and interactions. These investigations have unearthed the extremely complex nature of leptin's effects in the body and have quieted the initial enthusiasm that surrounded leptin's potential as a cure for obesity. The future may hold interesting possibilities for leptin as a therapeutic agent, but it is currently only indicated for individuals with leptin deficiency.
References
- "Arquivos Brasileiros de Endocrinologia & Metabologia"; Congenital Leptin Deficiency: Diagnosis and Effects of Leptin Replacement Therapy; G. Paz-Filho, et al; November 2010
- "International Journal of Obesity"; Leptin: A Review of Its Peripheral Actions and Interactions; S. Margetic, et al.; November 2002
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