Leptin Is a Protein Whose

Leptin is a protein whose expressions have significant implications in the current trends towards weight loss. Leptin is a relatively small molecule. It is a hormone, which like all hormomes is part of the ductless gland system -- recognized as the eleventh system of a mammalian body. The other systems are circulatory, digestive, immune, lymphatic, muscular, nervous, reproductive, respiratory, skeletal, and urinary. Its molecular weight is 16 kilo Daltons. The leptin gene is called Ob-Lep. The Ob stands for obesty; the lep stands for leptin. Leptin is found in adipose tissue, both the white and brown adipose tissue. Studies have shown that with weight loss from dieting and other factors, leptin amounts are reduced. Interestingly enough, the opposite effect is not observed when the behavior is the antithetical to dieting, over eating. (Castracane & Henson, 2006) The involvement of leptin in fat metabolism means that it is involved in the regulation of the expenditure of energy. In addition to fat tissue, leptin is also expressed in other tissues of the body, namely, the placenta, the breast epithelium, the bone marrow and the ovaries.

The crystal structure of leptin has been solved. The Protein Data Bank entry for leptin reveals two secondary structure features loops and alpha helices. There are four helices that are connected with intra-helical hairpin loops as well as a loop C- and N-termini. The PDB entry for this protein reads "Leptin -- the Human Obesity Protein."

ADDIN EN.CITE

(Zhang et al., 1997)

The protein crystallizes in the hexagonal space group and the unit cell consists of the protein as a trimer. It is interesting that leptin is identified as the human obesity protein. It was discovered in obese mice at the Jackson Laboratories. Jackson Labs. In Maine is a research institute where most of the work leading to the identification of the mouse genome was completed. Jackson hosts mouse colonies and supplies various strains to research laboratories everywhere.

Because of the expression of leptin in different parts of the body, the mechanism of leptin action is different. Leptin has a lot to do with the notion of hedonism. Therefore, this has a lot to do with the mechanism of leptin action in the brain, which has been well studied. The center associated with appetite suppression or appetite is in the hypothalamus. The leptin that flows in the blood crosses the blood-brain barrier and interacts with the region of the hypothalamus. The normal amounts of leptin binding with the hypothalamus results in proper appetite regulation. It was mentioned previously that overfeeding does not necessarily increase leptin. However, an overabundance of leptin in the blood and not enough that flows into the brain, results in inadequate binding in the hypothalamus. The lack of appetite suppression, thus results in over eating and therefore obesity.

There are other side effects to the reduced amounts of leptin in the brain. These are the same side effects to obesity. These include insulin resistance, high blood pressure, high cholesterol, metabolic syndrome X, diabetes, heart disease, thyroid problems, fibromyalgia, reproductive problems, sex hormone imbalances, increased risk for cancer, and increased risk for memory loss and Alzheimer's disease. (Bagchi & Preuss, 2007)

Leptin, its effects and relationship with metabolic issues, has given rise to a kind of diet that eschews the typical dieting programs. This is called the leptin diet and it aims to eat the sort of food that regulates the levels of leptin in the system. This has given rise to the "Five Rule" diet. The rules call for no snacking, restricting to three meals a day with about five to six hours between meals, eating a high protein breakfast, not eating after dinner, an restricting the intake of carbohydrates in the daily diet. It is important to remember that these diets are not related to loss of weight, but about the regulation of leptin levels. This is important to recognize: excess weight loss will result in lowering levels of leptin, which is not necessarily good as it upsets the balance of the hormones, which have been implicated in levels of other hormones too.

The imbalance of leptin to this plan is related to genetics. (J. M. Friedman, 2002) The storage of fat in a mammalian system is a genetic response to a time when humans had to go days before the next meal. The fat was a storage system to protect the body until the next meal became available. The same conditions however, do not apply today where for most of the world's population meals are regulated and regular. Therefore, the wrong diet, skipping meals affects the metabolism of fat, primarily because of the lack of maintenance of leptin levels in the system.

The slowing of metabolism or deliberately missing meals changes the level of leptins. The lack of leptin in the brain not only reduces its binding of the ventromedial nucleus of the hypothalamus, but exposes the brain to damage because it affects the NMDA receptors. (Richards & Richard, 2002) There is hence a risk of Parkinson's disease. It also leads to the accumulation of amyloid beta proteins resulting in plaques, which along with neurofibrillary tangles are implicated in Alzheimer's disease. Along with obesity related issues, the problems of ageing are also exacerbated.

Since fat metabolism is related to several issues, it affects several aspects of human growth. Fertility issues have been identified among male and female mice. If one were to project this to humans, the effects would be seen in puberty. Female puberty is closely linked to fat metabolism. If a pubescent teenager has problems with the regulation of fat, from issues such as anorexia or bulimia, then it is possible that the abnormal fat loss could result in the delay in the onset of puberty, as well loss of menstruation. Triglyceride levels can be affected by reduced levels of leptin; polycystic ovarian syndrome, which affects pregnancies in women. Morning sickness is also affected by leptin levels.

Because of the obvious needs of leptin regulation and obesity, several clinical trials have been conducted to find out the effects of leptin on several diseases. Administration of low dose leptin was tested in several patients, in a recently completed clinical trial. One of the salient results of the test was that some patients have a weight threshold, which even though at a higher than normal body to mass index do allow the body to function with normal levels of leptin. Altered weight levels are responsible for breaks in levels of leptin and obesity. The study was conducted at Columbia Presbyterian Medical Center in New York City. (Unknown, 2003) 25 patients, between the ages of 19 and 45 enrolled in the study, which was sponsored by the National Institute for Diabetes and Digestive and Kidney Disease. The aim of this successful study was the reduction of 10% of the weight of the enrolled subjects.