(Fig.1. The brown mouse's weight is more than thre times
than the normal black one.)*Leptin and leptin receptor:
Leptin was identified in 1994 originally by Jeffrey Friedmanë s lab in Rockerfeller University. It is a 16 kilo-delton protein, produced from obese (ob) gene of mice. If both two copies of this gene defect, the experimental animals act as perpetual starvation, unable to reproduce, and restrain their appetites. Thus, they grow grossly fat and weigh about 3 times compared with normal ones.(see fig.1)
(Fig.1. The brown mouse's weight is more than thre times
than the normal black one.)
The source of leptin comes from adipocytes, a kind of body fat cell. The adipocytes manufacture leptin and spew it into bloodstream. The amount of leptin secretion is proportion to how big the adipocytes get. These findings suggested that leptin functions as a lipostat: When fat stores rise, adipocytes produce leptin, and this hormone in turn tells the brain that itë s time to stop eating and increase energy using activity levels.
A year after, Louis Tartagliaë s team at Millennium Pharmaceuticals firstly clone the receptor gene in mice and humans. Some other investigators consequently also traced the diabetic (db) mice strain which mutant in the leptin receptor gene. In addition, Denis Baskin, at the Veterans Administration Puget Sound Health Care System, mapped the distribution of the receptors in four main regions of hypothalamus, including two--the arcuare nucleus and the paraventricular nucleus--that had previously been implicated as hot spots for the regulation of feeding and metabolism.
But interestingly, mutations in those genes do not seem to be at fault in human obesity, at least no one now identified a human being with a mutated Ob gene or ob receptor gene. Jose Caro, at Thomas Jefferson University, have found that the overweight people have high leptin concentration in bloodstream. One possibility is that leptin has problems making its way from the bloodstream into the brain because the spinal fluid of obese people contains only slightly more leptin than the normal one, despite more than fivefold concentration of this hormone in their bloodstream.
In 1997, the leptin structure was found in 3D structure, in Nature May, 8, 1997. (see fig.2) The definitional structure is helpful to design the anti-obesity drugs to against the undesired outlooking.
(Fig.2.Ribbon Diagram of OB protein, link to the fully page viewing.)
Alternatively, the brain may lose its ability to respond to whatever leptin does get in. One place to look is among the other molecules that interact with leptin to control weight, such as the potent appetite stimulating neurotransmitter called neuropeptide Y (NPY).
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