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Leptin: It's More Than Just A Fat Protein

When first discovered, leptin was thought to offer hope for treating obesity. But leptin seems to play a much more complex role, not only regulating food intake, but also influencing inflammation, insulin sensitivity, blood vessel development, and many other key functions.


Leptin is a protein made mainly by fat cells in the body. High leptin levels seem to be a marker of high levels of body fat. Leptin binds to receptors in the brain, resulting ultimately in a decrease in food intake; lower lipid levels in muscle, liver, and pancreas; and enhanced insulin sensitivity, bringing improved control of blood sugar. As you might expect, animals with low leptin levels are likely to become obese and to develop complications seen in obese human patients. Giving leptin to animals with low leptin levels can overcome the obesity and prevent the complications.


The picture is not so simple in humans, though. Although leptin deficiency accounts for some cases of obesity, resistance to the effects of leptin appears to be a more common cause of obesity. In such individuals, inability to respond to leptin (rather than lack of leptin) accounts for uncontrolled food intake and the obesity that follows. Leptin resistance certainly contributes to obesity, but leptin replacement in patients like these has been shown to reduce body weight only when given at very high doses, doses that may prove unsafe because of leptin’s other effects. Clearly, leptin is not a panacea for the majority of people who are obese.


In fact, leptin may contribute to blood vessel disease in obese individuals who are no longer able to respond to its effects on caloric intake and energy balance. It does so by altering blood vessel structure, influencing the development of new blood vessels, and increasing the risk of arterial thrombosis—cutting off blood supply to vital organs.


Besides its effects on food intake and calorie balance, leptin also induces the production of many other proteins (such as interleukin-6 and C-reactive protein) that participate in chronic low-grade inflammation in the body. In this way, high leptin levels (such as those seen in obese patients with leptin resistance) may be indirectly involved in the progression of obesity and its complications. On the other end of the spectrum, low levels of leptin may account for impaired immune function seen in patients suffering from malnutrition and starvation.


In some organs, leptin even has conflicting roles. In the intestine, for instance, leptin serves as a growth factor, enabling the cells of the intestine to make better use of carbohydrates and fats. At the same time, though, leptin also acts as a mediator of inflammation caused by the T lymphocytes that live there. A careful balance of these roles, then, is likely to be important in maintaining a healthy metabolism in the gut.


Scientists have only begun to understand the many functions of leptin. Recent research indicates that leptin regulates activities as diverse as neuroendocrine function and bone remodeling. Leptin may also play a role in the development of metabolic syndrome, itself a complex condition involving such abnormalities as insulin sensitivity, obesity, lipid abnormalities, high blood pressure, and inflammation.


Much more research needs to be done to define exactly what role leptin plays in the balance of metabolism and immunity. Might leptin someday find a place in the treatment of obesity? Could compounds that block leptin prove to be therapeutic in various inflammatory conditions? Can we safely influence the course of disease by modulating levels of leptin in the blood or tissues? Only time and careful study will tell.

Date Published: 03/12/2007
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