Obestatin, A Newly Discovered Appetite Suppressant Hormone
Researchers at the Stanford University School of Medicine
have recently announced they have discovered a new hormone involved in appetite control. Aptly named obestatin
, the hormone seems to have significant appetite suppressant effects
The story of the discovery is quite interesting. The researchers were looking for peptide hormones that might act on a certain type of cell receptors called G-protein-coupled receptor
, or GPCR. These receptors are activated by small molecule hormones, which makes them more attractive to drug manufacturers as it is easier to synthetize hormone-like substances with similar effects if the original hormone is small.
Data from the human genome project
indicates there are about 300 GPRCs. Of these, approximately 100 have no known hormone partner. After further analysis, they zeroed in on a specific DNA sequence found in several mammalian species, besides humans, which was known to code for another hormone, ghrelin. The big surprise was to realize that the product of this gene is a precursor of both ghrelin and obestatin
One gene coding for both ghrelin and Obestatin. Isn't this confusing?
was discovered a few years ago. It is a small peptide (28 aminoacids) produced mainly in the stomach. It's effect is to stimulate the secretion of the growth hormone from the pituitary gland. In addition, ghrelin induces sensations of intense hunger in humans. Another interesting thing is that blood concentrations of ghrelin are lowest shortly after consumption of a meal, then rise during the fast just prior to the next meal, which made it the subject of intense research during the last several years, in the hope that it may yield therapeutic agents against obesity.
Ghrelin is first synthesized as a preprohormone that needs to be further sliced by specialized enzymes and then chemically modified to become the biologically active ghrelin. As mentioned above, the same preprohormone that generates ghrelin can produce obestatin, too: it only needs a separate set of enzymes that cleave the obestatin sequence from it, and voila, instead of an appetite stimulant, hunger hormone, you end up with an appetite suppressant, satiety hormone!
I find this fascinating! On fist analysis, it seems confusing and counterproductive; it's almost like pressing the brake and the gas pedal at the same time. In reality, things are much more complex, and we are only beginning to understand the complexity of the energy regulation mechanism. Personally, I think there are important, designer-related reasons why ghrelin and obestatin are so closely inter-related.
- For one thing, it is a safety mechanism: should something happen to this ghrelin/obestatin gene, both hormones are knocked out. This has actually been observed in laboratory mice even before obestatin was discovered: mice with the ghrelin gene destroyed were not different in terms of body size than those with the intact gene.
- Having a common precursor producing two hormones with opposing effects on appetite may prove to be a very refined mechanism of appetite control..
What Are The Effects of Obestatin?
Injected with obestatin, normal weight mice ate about half as much as those given no obestatin. They lost about 20% of their body weight over an eight-day period. In addition, obestatin slowed the movement of digested food from the stomach into the intestines.
This is a major step forward in the field of obesity. A word of caution, though. Even though obestatin or some related compound may one day become a drug used to treat obesity, it is unlikely it will be a magic pill. Hopes have been high before in this field - remember the days when leptin
was discovered... Weight regulation is such a complex, redundant process that no single agent will ever be able to eliminate all the excessive weight. Besides, one should remember that, except for a very small minority, we are not becoming heavier due to obestatin or some other hormonal deficiency or imbalance. Overweight is primarily a lifestyle condition. Unless and until we are willing to correct our lifestyles by eating healthier and moving more, weight loss drugs can only offer second-hand solutions, at best.
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