Scientists find how obesity gene works, a clue to treatment

[webfact]

Scientists find how obesity gene works, a clue to treatment
By MARILYNN MARCHIONE

NEW YORK: -- Scientists have finally figured out how the key gene tied to obesity makes people fat, a major discovery that could open the door to an entirely new approach to the problem beyond diet and exercise.

The work solves a big mystery: Since 2007, researchers have known that a gene called FTO was related to obesity, but they didn't know how, and could not tie it to appetite or other known factors.

Now experiments reveal that a faulty version of the gene causes energy from food to be stored as fat rather than burned. Genetic tinkering in mice and on human cells in the lab suggests this can be reversed, giving hope that a drug or other treatment might be developed to do the same in people.

The work was led by scientists at MIT and Harvard University and published online Wednesday by the New England Journal of Medicine.

The discovery challenges the notion that "when people get obese it was basically their own choice because they choose to eat too much or not exercise," said study leader Melina Claussnitzer, a genetics specialist at Harvard-affiliated Beth Israel Deaconess Medical Center. "For the first time, genetics has revealed a mechanism in obesity that was not really suspected before" and gives a third explanation or factor that's involved.

Independent experts praised the discovery.

"It's a big deal," said Dr. Clifford Rosen, a scientist at Maine Medical Center Research Institute and an associate editor at the medical journal.

"A lot of people think the obesity epidemic is all about eating too much," but our fat cells play a role in how food gets used, he said. With this discovery, "you now have a pathway for drugs that can make those fat cells work differently."

Several obesity drugs are already on the market, but they are generally used for short-term weight loss and are aimed at the brain and appetite; they don't directly target metabolism.

Researchers can't guess how long it might take before a drug based on the new findings becomes available. But it's unlikely it would be a magic pill that would enable people to eat anything they want without packing on the pounds. And targeting this fat pathway could affect other things, so a treatment would need rigorous testing to prove safe and effective.

The gene glitch doesn't explain all obesity. It was found in 44 percent of Europeans but only 5 percent of blacks, so other genes clearly are at work, and food and exercise still matter.

Having the glitch doesn't destine you to become obese but may predispose you to it. People with two faulty copies of the gene (one from Mom and one from Dad) weighed an average of 7 pounds more than those without them. But some were obviously a lot heavier than that, and even 7 pounds can be the difference between a healthy and an unhealthy weight, said Manolis Kellis, a professor at MIT.

He and Claussnitzer are seeking a patent related to the work. It was done on people in Europe, Sweden and Norway, and funded by the German Research Center for Environmental Health and others, including the U.S. National Institutes of Health.

Obesity affects more than 500 million people worldwide and contributes to a host of diseases. In the U.S., about one-third of adults are obese and another one-third are more modestly overweight.

The FTO gene turns out to influence obesity indirectly, as a master switch that affects two other genes that control thermogenesis, or burning off energy. It's long been known that brown or beige fatty tissue — the so-called "good fat" — burns calories, while the more common white fat stores them. The body constantly makes fat cells, and the two genes determine whether they become brown or white ones.

In one experiment described in the medical journal, researchers blocked the faulty gene's effect in mice and found they became 50 percent leaner than other mice despite eating a high-fat diet, and burned more energy even when asleep.

In other tests on human cells, blocking the gene's effect increased energy burning in fat cells. Editing out the problem gene in human cells in the lab also restored normal metabolic function.

Researchers don't know the impact of having just one faulty copy of the gene but think it has less of an effect than having two copies.

Several companies are trying to develop treatments to stimulate brown fat, and the new research suggests a novel approach.

"It's a potential target" for drug development, said Dr. Sam Klein, an obesity researcher at Washington University in St. Louis. He called the work "an amazing study" and "a scientific tour de force."

Dr. Rudolph Leibel, an obesity expert at Columbia University in New York, used the same term — "tour de force." Still, some earlier research suggests the FTO gene may influence other aspects of obesity such as behavior and appetite.

"It's possible there are several mechanisms being affected," and that fat-burning is not the whole story, he said.


-- (c) Associated Press 2015-08-20

[puck2]

This "news" will generate hysteria. Eat a pill and .... (peng) you are slim. Nowadays everybody knows that especially chemical pills generate side effects.

This result is in a strong contrast to what I've seen and noticed advancing in years. Walking around in European and US states, watching TV or seeing the photos in newspapers you will recognize there are much more fat people around than in the fifties. It is aching to have a look at the fat faces, bellies, arms and legs.

Now - following the theory of these scientists - since the early fifties there must have been an unbelivable change in the genes, suddenly. Their theory also is in a strong contrast to what I notice every day. All fat people I know are not able to stop eating and drinking suggar-containing foods, fat meat etc. . When I'm already satisfied they start getting hungry.

And why do the people lose a lot of kilos when they change their eating and drinking habits? And why do they lose a lot of kilos if they start exercising? Genes of the same people are changing ?

I'm aware that the reason for this unproportional desire for food and sweet drinks may have a reasion in the genes, because not all people are getting fat when eating and drinking more than the other people on the table.

But it seems not credible that the genes of the fat people have changed so much in this short period until now. In general you see fat people in countries where the people earned more money than before, and are now able to eat and drink more than before. This is confirmed when you see the Thai top ranking police men in the medias. They seem not to have time for exercising, you cannot delegate the exercising job. And ordinary US police men are also not the leanest compared to their brothers in EU countries.

Edited August 20, 2015 by puck2

[NickJ]

Energy stored in fat. not as fat. In high energy carbon bonds. .......As I would think.

[little mary sunshine]

I can enlighten these "well paid" scientists.....Eating

Like a pig and no exercise makes you FAT !!

[Bakseeda]

Thailand is a wonderful example of thin to fat peoples... I came here first time in 1990. The peoples of Thailand were very slim and quite lovely peoples. They ate mostly rice, fish , lean meats and fresh vegetables which were plentiful. I still have videos I made in Bangkok and around many local markets and looking through those videos I can find almost no fat or chubby peoples. I cannot remember seeing one McDonalds or Burger King or Kentucky Fry.

Now 2015, 25 years on from my first visit and I have now been living here for 14 years full time . Fast food chains are everywhere, western style supermarkets with western style foods are part of Thai life now. And the result..... fat Thai people are plentiful, fat Thai people are everywhere but especially in the cities. Fat Thai people seems to be the normal thing now..

Oh well.... pass the hamburger and Chang please.........

Edited August 20, 2015 by Bakseeda

[ABCer]

A World famous Russian ballerina Maya Plisetskaya who died recently had her own advice:

"Eat less"

Most westerners could use this.

[soalbundy]

I can enlighten these "well paid" scientists.....Eating

Like a pig and no exercise makes you FAT !!

I thought it was the dress

[Jingthing]

It's great that modern science is continuing to make progress on expanding their knowledge and increasing the chances of offering safe and effective medical treatments to help fight the global obesity epidemic. Informed people (scientists) know for a fact it is not only a simple matter of morality and will power.

[Seastallion]

Oh dear Lord.....It's confirmed, now, that it's genetic.

One more handicap/disability that everyone is going to have to make allowances for....like airlines, employers, you and me....

I guess that sounds a bit callous....I am sorry for the FTO carriers, but there are bound to be obese people who are just lazy, greedy slobs and who do not have the faulty gene.

I think if it comes to it, people will have to prove that they've got the FTO gene to get treated specially. Otherwise, slobs without the gene will just take advantage.

[sandmike]

Has anyone done any research as to the effect on humans of the growth hormones that are fed to animals to bulk them up for market ??

Many links on your friend google ...

[Jingthing]

if science makes progress in understanding many kinds of human problems like cancer, diabetes, heart disease, STDs, etc. that are ALSO influenced by a person's individual behavior to various degrees (depending on the specific case) then DECENT people of good will applaud. But when the same thing happens in better understanding obesity, people get mean and disgusting and mock the people who are suffering with that problem. I call foul!

Basically, this is the deal, just like MOST human problems, obesity is complex and there are multiple factors that go into it developing and also tactics to reverse it. Free will choices are part of it but not the whole story. It is extremist to suggest it is ALL one or the other and careful readers of the article will see a balanced approach to this new advance that reflects that as well.

Edited August 20, 2015 by Jingthing

[AlexRRR]

if science makes progress in understanding many kinds of human problems like cancer, diabetes, heart disease, STDs, etc. that are ALSO influenced by a person's individual behavior to various degrees (depending on the specific case) then DECENT people of good will applaud. But when the same thing happens in better understanding obesity, people get mean and disgusting and mock the people who are suffering with that problem. I call foul!

Basically, this is the deal, just like MOST human problems, obesity is complex and there are multiple factors that go into it developing and also tactics to reverse it. Free will choices are part of it but not the whole story. It is extremist to suggest it is ALL one or the other and careful readers of the article will see a balanced approach to this new advance that reflects that as well.

If a fat person read that article they would have there excuse, its a cop out, the % of obese that is genetic is so low it hardly rates a mention....

Own up if your a comfort eater or just an out right pig but dont blame your genes for god sake...

For those who struggle its because you lack determination years of habit have formed you made you who you are today.

[partington]

if science makes progress in understanding many kinds of human problems like cancer, diabetes, heart disease, STDs, etc. that are ALSO influenced by a person's individual behavior to various degrees (depending on the specific case) then DECENT people of good will applaud. But when the same thing happens in better understanding obesity, people get mean and disgusting and mock the people who are suffering with that problem. I call foul!

Basically, this is the deal, just like MOST human problems, obesity is complex and there are multiple factors that go into it developing and also tactics to reverse it. Free will choices are part of it but not the whole story. It is extremist to suggest it is ALL one or the other and careful readers of the article will see a balanced approach to this new advance that reflects that as well.

If a fat person read that article they would have there excuse, its a cop out, the % of obese that is genetic is so low it hardly rates a mention....

Own up if your a comfort eater or just an out right pig but dont blame your genes for god sake...

For those who struggle its because you lack determination years of habit have formed you made you who you are today.

I find this response bafflingly obtuse.

How can anyone reading this account come to the conclusion that it is saying that obesity is all genetic (they state clearly that around 44% of caucasians have the faulty version, therefore 56% don't), or that what you eat is not important (they clearly state that the difference between people who have the faulty gene and those who don't is around 7 pounds, so this gene alone does not account for obesity)?

This again points out what I always notice about posters here: they are unable to comprehend that things have more than one cause, and all those causes can be equally important. So if someone announces a gene is important in determining obesity, the knee jerk reaction is to interpret this as saying this is the only cause of obesity, and then attack this non-existent straw man, that exists in their own heads only.

It has been known forever that different people consuming the same number of calories show different capacities to gain weight. The discovery of the function of this gene provides ONE explanation for this, Not the ONLY explanation, not even the most IMPORTANT explanation, but one factor among MANY that is going to be very significant.

I think this is really impressive. The possibility of increasing the amount or activity of brown fat to burn off more calories in a resting state is going to be a huge advantage, and this is the first step. However if you eat too much all the time, and do no exercise it's not going to help you that much!

There are no contradictions in this statement, and thinking there are shows incomplete understanding.

[JHolmesJr]

Theres no obesity gene just behaviour that promotes obesity....

Some time back a researcher released some info saying dark chocolate was good for you....and promotes weight loss....the guy was just kidding abt the weight loss but the media reported it without verifying.

[Jingthing]

Regardless of the headline, the study isn't saying literally there is an "obesity gene" but rather there is a genetic component that greatly increases the chances of developing obesity in some people. Good luck to the scientists to learn more that may eventually result in a safe effective clinical medical treatment that offers a high degree of success for many people. Right now, doctors don't have much to offer, except the morality lectures, and the truth is the morality lectures are not medically effective.

The consensus of studies I've read show that less than 5 percent (perhaps much less) of obese people attempting LONG TERM weight loss (like 10 to 15 percent of body weight which doesn't necessarily mean becoming not obese, just an improvement) do succeed. The "diet" industry is a multi billion dollar one, but for the most part, it's a total waste of money.

Any research that moves forward the day when doctors can actually offer their patients the chance of higher probability of good results is a GREAT thing in my book. But obviously, we aren't there yet.

Edited August 20, 2015 by Jingthing

[Neurath]

The ability to store energy as fat would be extraordinarily useful in a feast-famine environment, and people with this gene would have been selected over those burning the the energy rather than storing it. Would be interesting to see the historical and geographical distribution of the genetic traits. Genes distributed at different rates (environmentally determined) in all populations and environments so as to ensure that not all would be wiped out by famine like conditions.

Edited August 20, 2015 by Neurath

[Neurath]

The amount of effort being expended to move fat and obesity out of a moral environment and into a genetic one is immense. The same effort is certainly not being put into other addictions where the issue remains one primarily of moral economy. "You can't help fat but you sure can smack".

[Neurath]

The issue remains one of satiation. At a certain level of calorie consumption weight will be shed from ANY human body. Those with these genes would presumably need to eat less than others in order to maintain body weight and would presumably remain hungry - always. It may be a monumental effort of will to face off this hunger, but an issue of will it is. As it is with Junkies and alcoholics.

[robblok]

The amount of effort being expended to move fat and obesity out of a moral environment and into a genetic one is immense. The same effort is certainly not being put into other addictions where the issue remains one primarily of moral economy. "You can't help fat but you sure can smack".

Even with these figures it does not explain obesity. Fact still remains that they had only a 7 pound difference. That is not much at all. If you look at Thailand how people get obese and how they were not obese 20 years ago shows it is still caused mainly by overeating. Sure the other genetic things work against people.

I know that i got much more problems shedding weight and that I have to be far more careful as others, but when you know that you just accept it and make sure you stay on an acceptable level. The real obese guys have more as just a fat gene.. also they just overeat. Lifestyle is far more important as genes.

I am almost one of the long time success stories 4 years ago i lost 25 kg and kept it off. I do have my ups and downs but the moment I see weight going up I make sure I loose it again.

People with a love for food and the gene they just have to make choices accepting they are fat or change their love for food. Its all about priorities. My dad is also loosing more and more weight. Not by eating less but biking more 10.000 km so far this year (extreme for a 67 year old). My mother does not like her weight but only complains about it and never changes a thing. Guess what works better.

[Jingthing]

Obesity is not fully explained by science but it seems to me in the last decade more progress has been made than ever before. For example, the evidence continues to pour in that gut bacteria REALLY is a factor in the global obesity epidemic. Yes we've had gut bacteria through the ages but only in modern times was it challenged by antibiotics and industrialized processed foods. So yes lots of great research is happening, and no, this has not yet resulted in an effective medical treatment that really works for the masses, but that doesn't mean it won't eventually. I'm pretty sure that it will but then the question will be the cost and access to the people that need it. Also as stated in the OP, even having an effective medical treatment doesn't mean people will EVER be able to eat all they want of any foods they want, that's a given.

Really, there is a long list of complex factors that contribute to person's obesity.

Will power is of course ONE of them.

But so many others, for example:

Food environment

Nutrition education

Access to affordable healthier foods

Stressful conditions / poverty creating environments where filling the tummy with ANYTHING is all that matters

Cultural factors (some national food cultures feature unhealthier foods, such as the American south)

Urbanization

Thyroid hormone deficiency

Wide availability of cheap processed foods filed with obesity promoting ingredients

Lack of warning labels on food

Biology of fat cells

How being an obese child changes biology for life (small chance of reversing in adulthood)

Sugar addiction

Gut bacteria issues

Genetic issues

Social stigmatization of obese people contributing to depression promoting even worse obesity.

Edited August 20, 2015 by Jingthing

[Neurath]

If you're obese and you don't have these genes, does this make you a moral failure (assuming you don't want to be obese)?

Perhaps this discovery will result in differential treatment for obese people:

1. Those for whom the obesity is a genetic. Obesity not a moral issue for this lot. Not failures, just sad people with bad luck.

2. Those for whom the obesity is not genetic. Obesity a result of gluttony and lack of self control. Obesity a moral issue for this lot. Sad people who brought misfortune upon themselves. Should be ashamed of themselves really.

Perhaps there should be disabled parking spaces only for the genetically obese and insurance rate punishment for the volitional obese.

Of course, those who have the genes but are not obese should be lionized as the moral champions they so clearly are. "My body tries to Sin against me, but I have overcome the temptation of the flesh Lord!!! I have denied myself and won!!!" After all, our modern times are characterized by a wild vacillation between cacophonous demands that we deny ourselves and that we indulge ourselves. Can make one quite dizzy really.

[Jingthing]

There are complex factors.

This study was about a gene.

Other studies are about other factors, such as gut bacteria.

Like many complex problems there won't be a one size fits all solution that works for all people.

But increasing success rates above the 1 to 5 percent we have now is definitely achievable with the help of scientific advances in the not too distant future. I am very confident about that.

[Neurath]

These genes seem to allow for the body to run more efficiently. That is, allow the body to store more energy from the same number of kilo calories than would be the case for someone without these genes. Suggesting that, genetically speaking, slim people are gas guzzlers burning up whatever is put into their tank.

Anyway, all levity aside, it still comes down to satiation and the 'ability' to tolerate always feeling hungry. Just like it does for recovered/recovering smack addict.

Remove temptation and you remove sin, remove sin and you remove redemption. Remove, temptation, sin and redemption and you remove Dostoeyevsky.

[partington]

The major point here is that now that the function of this gene is known, and the metabolic pathway it regulates has been identified, this supplies a target for drug development.

Nowadays drug development is largely carried out by

1. Identifying a molecular target that you can decrease or increase the activity of to have a beneficial effect on a disease process

2. Finding a drug to do this, usually by isolating the molecular target and seeing what chemical compounds bind to it.

Nearly all biology works by key and lock mechanisms at a molecular level. For example, a protein can be activated by a hormone which recognises its 3D shape by itself having a 3D shape that binds to (fits into) the protein.

Drugs are chemical compounds that interfere with or enhance biological functions by also having the correct 3D shape to bind to molecular targets. Once you know your molecular target you can simply test a million random compounds to find ones that bind to it, and these are likely drug candidates.

So this is the importance: it gives scientists a directed way to find anti-obesity drugs. These will work on people with or without the defective gene. The finding of the faulty gene tells them how to start developing a drug, by telling them exactly what molecule they need the compound to bind to.

[Rancid]

It's great that modern science is continuing to make progress on expanding their knowledge and increasing the chances of offering safe and effective medical treatments to help fight the global obesity epidemic. Informed people (scientists) know for a fact it is not only a simple matter of morality and will power.

Hmm, modern science is only interested in making money, and that is done through offerring expensive pills with often dangerous side effects so the lazy and ignorant can avoid the "hard choices" that would actually improve their overall health.

Most diseases are lifestyle related, if you are waiting for a cure in a pill you will be waiting a long time. That is why despite the billions poured into cancer there is no cure pill. However, to each his own lifestyle choice.

[up-country_sinclair]

Let's speak frankly: these fatsos shouldn't blame anyone or anything except their own disgusting gluttony.

Let's keep in mind that obese is generally categorized as someone who is 30 pounds overweight. 30 Lbs! That's a lot of trips to the drive-thru at McDonalds (sure, Super Size it!), phoning for pizza delivery (undoubtedly with extra cheese) and having more ice cream in your freezer than a Baskin Robbins shop.

Stop looking for something to blame and start getting at least 30 minutes of exercise a day.

Stop thinking it's not really your fault and start consuming only 2000 calories a day.

It will be a scientific miracle when you're much thinner in a few months.

[pedro01]

The only thing going on here is to get fatness classified as a medical condition.

Then all treatments need to be FDA approved.

So drug companies can corner the fatness market

[Jingthing]

Perhaps some people don't realize this, but the New England Journal of Medicine is a very highly respected publication.

http://www.nejm.org/doi/full/10.1056/NEJMoa1502214?query=featured_home#t=articleTop

In summary, our work elucidates a mechanistic basis for the strongest genetic association with obesity. Our results indicate that the SNV rs1421085 underlies the genetic association between theFTO locus and obesity. The SNV disrupts an evolutionarily conserved motif for the ARID5B repressor, which leads to loss of binding, derepression of a potent preadipocyte superenhancer, and activation of downstream targets IRX3 and IRX5 during early differentiation of mesenchymal progenitors into adipocyte subtypes. This results in a cell-autonomous shift from white adipocyte browning to lipid-storage gene expression programs and to repression of basal mitochondrial respiration, a decrease in thermogenesis in response to stimulus, and an increase in adipocyte size. Manipulation of the uncovered pathway, including knockdown or overexpression of the upstream regulator ARID5B, genome editing of the predicted causal variant rs1421085, and knockdown or overexpression of target genes IRX3 and IRX5, had a significant effect on obesity phenotypes.

We're not talking Dr. Oz here.

Personally, I'll just ignore the mean spirited comments of haters who clearly don't have an ounce of understanding or compassion for people dealing with obesity.

That on top of being ignorantly HOSTILE towards scientific research on obesity. That's their problem. Science moves forward IN SPITE of such regressive haters.

Edited August 20, 2015 by Jingthing

[Jingthing]

More on the POTENTIAL future implications of this groundbreaking research ... in non-scientific language:

http://www.nationmultimedia.com/breakingnews/Obesity-master-switch-in-genes-may-be-turned-off-s-30267036.html

Then, they showed that they could manipulate this new pathway to reverse the signatures of obesity.

Using a DNA editing technology known as CRISPR/Cas9, researchers could switch between lean and obese signatures.

When researchers inhibited the corresponding gene in the fat cells of mice, the animals’ metabolism soared and they shed weight without eating less or exercising more.

"The results at the organism level were dramatic," said lead author Melina Claussnitzer, a visiting professor at MIT.

[Seastallion]

More on the POTENTIAL future implications of this groundbreaking research ... in non-scientific language:

http://www.nationmultimedia.com/breakingnews/Obesity-master-switch-in-genes-may-be-turned-off-s-30267036.html

Then, they showed that they could manipulate this new pathway to reverse the signatures of obesity.

Using a DNA editing technology known as CRISPR/Cas9, researchers could switch between lean and obese signatures.

When researchers inhibited the corresponding gene in the fat cells of mice, the animals’ metabolism soared and they shed weight without eating less or exercising more.

"The results at the organism level were dramatic," said lead author Melina Claussnitzer, a visiting professor at MIT.

With circa 20 000 protein-coding genes in humans, I would not take a drug that "switched" a gene on or off......what other genes are being affected by the drug, what other effects that may not be obvious in trials?

No thank you.