Fighting obesity: Cheat the Hunger hormone
Blocking the enzyme that activates ghrelin, the "hunger hormone", caused weight loss in laboratory mice. A new approach may someday lead to the development of drugs to treat obesity in humans.
Currently, the annual turnover of the anti-obesity drugs market is about a billion US dollars, to one degree or another, about 300 million people regularly take these drugs. Currently, the efforts of developers of new drugs that suppress hunger are aimed at creating synthetic analogues of hormones secreted by the cells of the digestive system in response to an increase in blood sugar levels. Some of these artificial hormones are already used in the treatment of diabetes.
Philip Cole and colleagues from Johns Hopkins University, the University of Cincinnati and the National Taiwan University decided to bypass the feeling of hunger from around the corner by blocking the work of a link in the biochemical pathway preceding the activation of ghrelin, known as the "hunger hormone". The transition of ghrelin to the active form occurs under the action of another enzyme, ghrelin-O-acyltransferase (ghrelin O-acyltransferase, Goat), under the action of which an octocarbon carboxylic acid is attached to one of the serine fragments of ghrelin. Unacylated ghrelin does not cause hunger.
The researchers decided to develop a molecule capable of binding to the same sites of the Goat enzyme with which ghrelin interacts. The resulting compound – GO-CoA-Tat – contains a fragment of ghrelin and octanyl-coenzyme (octanyl-CoA), which includes a residue of the same octocarbon carboxylic acid, which converts ghrelin into an active state. A molecule containing two of Goat's most important substrates turned out to be able to specifically bind to its active center and block not the "hunger hormone" itself, but its activator.
GO-CoA-Tat injections resulted in weight loss in normal mice. Genetically modified mice with a reduced level of ghrelin synthesis did not lose weight from such injections, which confirms the assumption about the mechanism of action of GO-CoA-Tat.
The results of the work (Barnett et al., Glucose and Weight Control in Mice with a Designed Ghrelin O-Acyltransferase Inhibitor) are published in the journal Science.
John Wilding, an obesity specialist from the University of Liverpool, notes that the approach implemented in Cole's group is very promising, although the development of an anti–obesity drug is still far away, including because it is currently virtually unknown how long-term suppression of ghrelin activity, which not only causes hunger, but also affects growth functions and possibly play a role in memory-related processes.
Portal "Eternal youth" http://vechnayamolodost.ru according to the Royal Society of Chemistry: 'Hunger hormone' activating enzyme holds promise as obesity target.
24.11.2010