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Is Leptin a Weight Loss Hope? 1: The Theory
We do have a homeostasis for body weight, which means your body works hard to maintain the weight it considers the best for you. But what if what it thinks is wrong?
Is anything wrong with our culture that causes the problem of overweight? Or has the wrongdoing been already done long ago when fat storage in the human body stopped being a mean of survival of the species? In animals, it is an advantage to be able to store energy in the form of fat (or better to say, of triglycerides in adipose tissue). The triglycerides are energy dense and easily available for mobilization to meet energy needs in the times of food shortage.
The sweet taste and soft oily texture of foods are meant by Nature to signal to the brain that the energy dense fuel has became available (fruits are ripened or the game gained some fat) and it's time to eat more. We will be discussing soon how the taste of food influence the body weight set point - the tastier the heavier.
Does it mean a lack of willpower on our part? Of course, during complete fasting or on a very low calorie diet, no miracle happens: the body burns the fat for fuel. However, this concept from a scientific view point is considered unsatisfactory. At least willpower (or environment) is only one part of the problem. Twins, adoption, and animal models studies confirm that genetic makeup influences obesity significantly (N. Eng. J. Med., 322:1520-4, 1990). Another fact in favor of strong automatic controls that are beyond our willpower is that of diet failure in the long run and that the thin and the fat do maintain their weight though at different levels. But what exactly makes the levels so dramatically different?
The very fact that the mechanism works means it has a feedback loop. For years, scientists argued about the physical nature of this feedback. The candidates were: blood glucose, lipids, body temperature, stomach distention, gut hormones, circulating amino acids and many more (Cell, 87:377-89, 1996). Nobody ever proved these are not components of the feedback loop. However they are all components of only short-term regulation. Also, nobody has explained why they work differently for the thin and for the fat. Until recently.
The gene of obesity was shown to be responsible for producing a hormone named Leptin, from the Greek word leptos=thin. This gene is mutant in genetically obese mice that weight three times as much as normal controls even fed precisely the same diet. It was supposed that Leptin was a signal in the feedback loop that regulate how much fat should be stored and how much burned.
Leptin Study at Duke medical school allowed the conclusion:
Leptin appears to be a sensor of fat cell size, so that when the cell reaches a certain proportion, it sends a signal that elicits some metabolic response to eliminate fat.
Indeed, injections or better yet permanent subcutaneous (under the skin) infusions of Leptin has decreased the body weight -- the more the higher the dose was. Leptin levels in the blood plasma increased, too, but remained within physiological normal range (Proc. Natl. Acad. Sci. USA, 94:8878-83, 1997). What's more, unlike most efficient weight loss methods, it spared the lean body mass (Science, 269: 543-6, 1995).
Leptin concentration in the blood does not increase after a meal. It only increases (normally) when the amount of stored fat increases, thus the mechanism of long-term body weight regulation was finally realized!
Besides, it turned out that Leptin acts in a good coordination with many of the well known agents of eating behavior like appetite suppressing the hormone Cholecystokinin, body temperature, or hypothalamic control of hunger: Leptin influences them and they influence Leptin. Mutations in Leptin present in hypothalamic neurons result in obesity.
So far so good. But how about us humans? What does Leptin promise in our battle with obesity?
- More information:
Molecular and anatomical determinants of central leptin resistance
Leptin is produced in proportion to fat stores; adequate leptin levels communicate the repletion of body energy stores to the CNS in order to suppress food intake and permit energy expenditure
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