A gene that makes people vulnerable to obesity also produces a protein that may directly modify DNA in a region of the brain known to control food intake. The unexpected finding sheds light on how gene variants can predispose individuals to obesity, say scientists. Earlier this year, analysis of blood samples from nearly 40,000 individuals linked certain variants of a gene called FTO with a 70% increased risk of obesity. Those people who carried two defective copies of the FTO gene were 3 kilograms heavier on average than their counterparts with normal versions of the gene. Ashcroft and her colleagues synthesised the FTO protein in the laboratory using the human sequence and mixed the protein with single-stranded DNA in a test tube. They found that the protein removed chemical markers on the DNA, known as methyl groups. This is significant, as the addition and removal of methyl groups can act to switch genes on or off, so altering their activity. This process is known as 'epigenetic' change. The researchers believe that the FTO protein may somehow modify the activity of genes involved in metabolism and fat storage, which in turn may influence a person’s risk of obesity. In another part of the new study, researchers examined the brains of mice designed to produce fluorescent FTO proteins. They found high concentrations of the protein in the rodents' hypothalamus, a region of the brain that helps regulate hunger. Ashcroft says it is still unclear how the FTO protein directly influences appetite, but it could possibly be exerting influence by altering the activity of other genes. Alan Herbert, a geneticist at the Boston University School of Medicine in Boston Massachusetts, US, says that certain FTO variants might work in the brain to increase fat storage throughout the body. But he stresses that these variants could have been helpful for our ancestors, who had less reliable food supplies: "At some point in history, it was likely advantageous to efficiently store calories." http://www.newscientist.com/article/dn12893-obesity-gene-may-alter-brain-dna.html
Yes. Methylation is addition of a methyl group to a region of the DNA, typically in a CpG site (cytosine and guanine separated by a phosphate) and results in inhibition of transcription; this is either by physically impeding the binding of transcriptional proteins or (as also seen in cancers) by the binding of methylated CpG's by methylated CpG binding domain proteins (MBDs). The MBDs then recruit histone deacetylases that modify the histones binding the DNA and make a compact inactive chromatin, that is "silenced" by an inability to undergo transcription. Its of great interest in epigenetics. Here is a good reference http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=AbstractPlus&list_uids=12154400
Thanks, very informative. So, what is your opinion on the significance of the research? I.e., how worthwhile is it to learn about this rather than just putting these people on a diet? Please Register or Log in to view the hidden image!
If demethylation of a known gene is a cause of the uncontrolled appetite and fat storage in extreme obesity, the use of techniques that bock its demethylation by reducing the expression of the FTO protein variant (by using anti-sense oligos for instance)may be more useful for those who are unable to control their own appetites. How worthwhile is it? It offers a doable choice for those who are genetically vulnerable.
Are there actually people with "uncontrolled appetite"? It's hard to imagine since I have no common frame of reference. To attempt to get one, would you say it is more uncontrollable than someone with a case of the munchies?:m:
When discussing obesity and weight gain in U.S. and the rest of the world, people often forget the effect of birth control pills and hormone levels in dairy and meat products; these would mostly affect women, of course, but these factors are reasons for a good percentage of obesity cases.
We all have a form of control of regulation of energy balance in the body, both short term and long term. e.g. overeating a slice of bread (50 kcals) over 10 years would gain you 20 pounds. The ability to balance this delicate difference is suppressed in obese people.
If you want to lose weight you merely don't eat as much. No-one walked out of Auschwitz looking overweight apart from the German Guards.
And this might be very good for certain individuals, but just to react to the seemingly logical process of finding a genetic predisposition ----> solution route often followed in these situations: I think we end up pathologizing individuals rather than looking at societal problems that end up causing problems displayed by certain predisposed individuals. (not something I expect you do very much SAM, but I am responding to the pattern in the thread). We have a tendency to shift from thinking of predispositions as causes and then there is a trend, supported by profit making urges in pharmaceutical companies to add the definitive 'the' before that cause. Making it 'the' cause. Societal contributions related to stress and nutrition - as two examples - are not addressed, but we find solutions that help us adapt to society. (This trend is rather more pernicious on the psychotropic medicines end of things) Instead of making a society that fits us we are shifting to finding methods to shift us to fit society. Gene modification will make this even easier.
<< And this might be very good for certain individuals, but just to react to the seemingly logical process of finding a genetic predisposition ----> solution route often followed in these situations: I think we end up pathologizing individuals rather than looking at societal problems >> Societal problems? Have you seen the weight of Parliaments...the House of Commons front benches are so overloaded they sag in the middle.
True; I like to think of it as part of a larger scheme. e.g. if someone is genetically vulnerable, the environment they grow up with has a lot to do with their final outcome. Genetic protection or susceptibility is not absolute (except when one talks about some diseases), but its part of the puzzle when we hit a wall in treatment. ie, if you go on a diet, you may lose the first five pounds due to changes in your regimen, then find the next five impossible to lose. This may not matter much if you are a 110 pounds but will be a matter of concern if you are 300 lbs. Knowing what else goes into the puzzle then becomes a necessity.
I think sometimes even positive genetic traits - or traits that add to a positive diversity of temperments and skills - are seen a traits to be treated.
<< If you go on a diet, you may lose the first five pounds due to changes in your regimen, then find the next five impossible to lose. >> Well thats something of a myth in reality, especially if you're 300 lbs. All it suggests is that after losing a sudden amount of 10lbs you become hungrier. Eureka!
