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Leptin is a hormone that sends signals to the brain to relay whether the body is nourished or starving. For these signals to be transmitted, there must be a molecular switch on the appropriate brain cells to receive the signal. Such switches are proteins known as receptors. There are a number of such leptin receptors that respond to the molecule. Other tissues besides the brain can respond to this compound, and there are a variety of forms of such receptors in the human body.
While insulin has been known as a hormone affecting energy metabolism since the early 1900s, leptin was only discovered in 1994. When the body’s hormones are working properly, it signals the brain when the body has enough energy. Originally postulated to be a new way to help people to lose weight, its effects have been found to be profoundly more complicated than expected. Many different tissues in humans have leptin receptors, and the compound produces a myriad of effects on human physiology.
The original discovery of leptin was from mutant mice that were highly obese. They were found to lack the gene to produce the compound or the receptor. In mice, the gene for the leptin receptor is known as db. Genetic studies showed the genes for the hormone and its receptor to be highly conserved between organisms.
In humans, the gene for the leptin receptors is known as LEP-R. There is a small group of people in the world that suffer from a mutation in this receptor. Morbid obesity is the result of this mutation.
To be able to carry a signal from outside of the cell to the interior, the receptor must cross the cell’s plasma membrane. Many receptors have a series of loops within the membrane. The leptin receptors only have one domain through the outer cell membrane into the interior of the cell. When leptin binds to the surface of the receptor, it activates a change in the structure of the receptor inside the cell. This causes a cascade of signaling, resulting in changes to hormonal metabolism.
One product is produced from the gene, but it is processed into many different types of leptin receptors during the process of being modified from DNA to its final protein form. These receptors vary in the length of the protein that extends within the cell. The brain receptor that responds to signals from the fat-containing adipose tissue differs from the other ones by having a long extension of the protein within the cell. Some forms of the receptor have been found to be soluble and not connected to the cell’s membrane.
More recent research has shown that leptin has effects on the metabolism of other tissues, including the lung, kidney, and prostrate. The leptin receptors in these areas have much shorter intracellular regions. Some studies have implicated this hormone in the development of certain cancers. Future research will undoubtedly reveal a great deal more about additional effects of this hormone on human physiology.
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