Researchers believe they have touched why a common obesity gene causes weight gain: those who carry a version of it n 't feel full after eating and taking in extra calories. Indeed, the variation of OFL gene in question, one on six individuals wear, leads to higher levels of ghrelin, a hormone involved in the mediation of the appetite and the body's response to food, the researchers found. While most studies FTO relied on mice, the new work has analyzed samples of blood and human brain scans.
"This is a very exciting piece of research," says geneticist Andrew Hattersley of the Peninsula Medical School in Exeter, UK, who was not involved in the new study. "There much work has been done on the FTO mechanism in animals, but be careful in applying these lessons to people. So it's nice to finally see the work done in humans. "
Hattersley was part of a team that in 07 reported that people who have had a version of FTO gene, called AA, weighed an average of three kilograms more than the TT version of the gene. Since then, studies in mice have shown that in all, there are high levels of the protein FTO in areas of the brain that control energy balance. the researchers also found that animals with AA Version tend to eat more and prefer foods high in fat compared to those of the version TT. But why FTO this effect was not known.
Rachel Batterham, a researcher in endocrinology and obesity at University College London, thought the gut hormones involved in the body's response to food could be the missing link between FTO and food intake. One such hormone ghrelin is known to be produced by cells of the gut to stimulate hunger. Then Batterham et al ghrelin levels measured in blood nonobese men with AA or TT versions of OFL . In those with the TT variant, ghrelin levels rose before a meal, when the person has experienced hunger, and fell after eating, as expected. But in those with the release of obesity associated with AA, ghrelin levels remained relatively high, even after eating. In addition, AA individuals reported a faster increase in hunger after a test meal. And MRI showed that when test subjects were shown images of food before or after eating, the brain activity in areas associated with motivation and reward remained high before and after meals in AA people. This suggests that increased ghrelin levels affect the brain's response to food, which "corresponds very well with what we already know the effects of ghrelin," says Batterham.
But could higher levels ghrelin unrelated FTO? the researchers do not think, in part because they have found that in isolated human cells, increased FTO protein levels led to increased production of ghrelin. the reason this occurs, the group has shown, is due to the fact that the FTO protein actually changes the gene for ghrelin, which causes methyl chemical groups to eliminate a so-called epigenetic modification that impacts the amount of protein gene ghrelin product. the variant of the AA gene, the researchers report online today in the Journal of Clinical Investigation removed more methyl groups from the gene, which leads to increased levels of 'hunger hormone.
Whether this proves true, the story is FTO remains uncovered, Hattersley said. "What we do not know is whether FTO that changes many things that affect appetite, ghrelin which is only one," he said. "I suspect the human appetite and obesity is more complex than a single hormone. "
neurobiologist Tamas Horvath of Yale University agrees. "This is a beautiful piece of work at face value," he said. "But I think it is reasonable to continue to pursue other avenues to see what could happen here."
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