Scientists discover mechanism that could reduce obesity
December 12, 2012
Laboratory mice (credit: Lightmatter/Wikimedia Commons)
An international team of scientists led by Virginia Commonwealth University Massey Cancer Center researcher Andrew Larner, M.D., Ph.D., has successfully reversed obesity in mice by manipulating the production of an enzyme known as tyrosine-protein kinase-2 (Tyk2).
In their experiments, the scientists discovered that Tyk2 helps regulate obesity in mice and humans through the differentiation of a type of fat tissue known as brown adipose tissue (BAT).
Approximately 68 percent of U.S. adults are overweight or obese, according to the National Cancer Institute, which puts them at greater risk for developing cancer, cardiovascular disease, diabetes and a host of other chronic illnesses.
The study is the first to provide evidence of the relationship between Tyk2 and BAT. Previous studies by Larner and his team discovered that Tyk2 helps suppress the growth and metastasis of breast cancer, and now the current study suggests this same enzyme could help protect against and even reverse obesity.
The scientists were able to reverse obesity in mice that do not express Tyk2 by expressing a protein known as signal transducer and activator of transcription-3 (Stat3). Stat3 mediates the expression of a variety of genes that regulate a host of cellular processes. The researchers found that Stat3 formed a complex with a protein known as PR domain containing 16 (PRDM16) to restore the development of BAT and decrease obesity.
“We discovered that Tyk2 levels in mice are regulated by diet. We then tested tissue samples from humans and found that levels of Tyk2 were more than 50 percent lower in obese humans,” said Larner, Martha Anne Hatcher Distinguished Professor in Oncology and co-leader of the Cancer Cell Signaling program at VCU Massey Cancer Center. “Our findings open new potential avenues for research and development of new pharmacological and nutritional treatments for obesity.”
There are two different types of fat — white adipose tissue (WAT) and BAT. WAT is the primary site of energy storage. BAT is responsible for energy expenditure in order to maintain body temperature. BAT deposits are present in all mammals, but until recently, scientists thought BAT was only active in infants and not in adult humans. Only in the last four years have scientists realized that BAT is present in adults and helps to regulate energy expenditure.
Research has also shown that diminished BAT activity is associated with metabolic syndrome, a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes. Researchers estimate metabolic syndrome could affect as much as 25 percent of the U.S. population.
“We have made some very interesting observations in this study, but there are many questions left unanswered,” said Larner. “We plan to further investigate the actions of Tyk2 and Stat3 in order to better understand the mechanisms involved in the development of brown adipose tissue. We’re hopeful this research will help lead to new targets to treat a variety of obesity-related diseases such as cancer, cardiovascular disease and diabetes.”
This study was supported by National Institutes of Health grants R01 AI059710-01 and R21 AI088487, the Austrian Science Fund and, in part, by funding from VCU Massey Cancer Center’s NIH-NCI Cancer Center Support Grant P30 CA016059.
Comments (34)
by Joe Cash
Wish I could change what it is that I want. I wish I didn’t want sausage pizza, ice cream and candy. I wish I wanted much less salt than I do. Same with bad fats. It would still be me, because I made the choice to change myself. Wish I could change myself so that my primitive appetites matched what I intellectually think is desirable.
by PirateRo
Ha! I would have said pizza with ‘srooms and sausage and extra cheese, orange crush, ice cream, Hershey’s chocolate with almond bar, nerds and smartfood popcorn to go with my 20+ hours of Netflix weekend viewing…
by PirateRo
Oh, and orangey cupcakes with the orangey frosting from hostess but I guess I don’t have to worry about those any more…
by Tony Stender
If we look at the problem carefully, it has only recently been happening.
There are a lot of bright folks reading these postings Ray has been kind enough to make available for us.
If you were able to make a prediction of the various causes, the question seems to become: what happened within that time frame which might account for this phenomenon to occur. I would be interested in what kind of responses your collective intelligence might offer up as to the possible causes of this problem.
I am guessing that there might be some designed corporate profit making included as part of the causes offered up. Perhaps they might be considered as an easy part of the solutions, which might be easily reversed.
by melajara
There is not ONE primary cause or one conspiracy for this evolution but rather a conglomerate of self supporting relations promoting in fine this sad end result.
However to make a long story short about the (ab)use of sugar, let’s say that there is corporate greed on one hand (supply) and addiction on the other (demand).
To develop a bit the story, lets say that at the beginning the addition of sugar to mass marketed food was initiated because sugar is a very good conservative agent easily available and at low cost. In mass markets, and even more now in the age of globalization, the spatial distance and time from production to actual consumption is widening, hence the importance of the conservative agents as mandatory ingredient of everyday’s food is proportionally increasing too.
Besides, sugar (the refined form) has the very interesting property to be an addictive substance, so it’s a win-win situation for producers. By extending the product durability before peremption, producers are simplifying the logistic of production and lowering their costs.
In the same time, the consumers progressively become addicts and are craving for the poisonous products. A critical mass (pun intended) of citizens are asking for those products forming a self sustained vicious circle stabilized by a social consensus of common acceptance of such products.
Now government could act as a regulator of public health, breaking the vicious circle, but we very well know that in a simili democracy which derived to an hypocrite plutocracy, lobbying is everything. Thus the major producers successfully lobbied to evade bills to enforce a reasonable limit on the use of sugar in everyday mass marketed food nor do the poisoned mass of citizens were asking for it, then no political figure got elected with the promise to eradicate the tyranny of sugar on the table, LOL.
It is only recently that global obesity is taking such a toll among the population that the problem begins to be recognized and, hopefully, will be progressively addressed.
by mark lewis
in 1990 UC Santa Barbara, one of my psych professors (Ettinberg, I believe) was studying how to increase BAT activity in adult humans for weight loss purposes. The challenge? Everything that worked amped up the CNS so much that it whacked out the whole system. Not good.
I have been following this research since then, and it all sucks. Great idea, no real progress. Perhaps this tyrosine bit will make the difference. I hope so!
So, the “only in the last 4 years” comment is, perhaps, overstated.
by asiwel
There is a common philosophic problem here. “Preventive” has come to mean “don’t do what you want to do” rather than “do what you want while avoiding consequences.” I am pretty much for the latter. I do not want to HAVE to “eat right, exercise, and stop smoking” in order to live forever. I would much rather a robot tilled the field (or a person who loves farming) rather than me. Science, technology, “knowledge” – are supposed to be empowering, not depressing. I tend to agree with Dr. Faustus. It has always seemed to me that there are many ways social norms and cultures can change (for the better) while still fully absorbing technological and medical progress (and still ensure “profits” – for every one.) Race with machines, not against them. Heck, that’s even NASCAR philosophy. John Henry was noble for sure, but a bit misguided.
by Mr.X
asiwel: Some more whine with your cheese!? Oh wait, too many calories.
Seriously, although I disagree with your view in so far as I think it is good not to always become what you want (hedonic adaptation); I guess that you perils, depending on your age, will be over sooner or later.Either you die or technology will solve these problems, or at least greatly alleviate your “suffering”.
by asiwel
Ha, One would sure hope so … for one of the latter two eventualities at least! And, yes, it is not always a good thing to get what you want. But, seriously, a technological “fix” here and there can often change the paradigm for arguments about “cultural vices and virtues” that have gone on without satisfying resolution for decades (drug wars) or centuries (victimless “crimes” in general) or even millennia (gluttony).
by Mr.X
Honestly, I think this is for losers.If one is to weak-willed not to buy and eat garbage, he’ll get what he deserves.
by Mr.X
Or she, to be fair.
by Robert H. Pike
Rude and mean to call people suffering from eating disorders “losers”. Look at it this way; they were raised, before they could talk and walk, to shove something in their mouth to get emotional satisfaction. They are suffering a profound addiction that was really caused by well meaning parents. Don’t be so crude and rude. Have pity for those suffering this addiction that they didn’t start.
by Azryan
I think you go too far to imply that all fat people are helplessly conditioned to be that way from birth, and even as teens and adults, can do nothing about it of their own volition. My dad died from essentially getting too damn fat, but none of his brothers and sisters were fat. He knew he was killing himself and just didn’t bother to care and put in the effort to lose the weight. It wasn’t bad genetics or how he was raised. He was a glutton in lots of different ways beyond food.
Overeating may be a type of ‘addiction’ (this is not ‘hard science’), but it isn’t the same type as say heroin or nicotine. Not only is there no chemical dependency, but if you actually quit entirely, you starve to death. They just need to stop when they’re full and exercise more than ‘not ever’. This is the main failing is nearly all of these cases. I have pity, but I think you have too much.
But hey, maybe a stupid pill will magically solve it for them. They’ll probably complain about the cost.
by Mr.X
@Azryan: “I think you go too far to imply that all fat people are helplessly conditioned to be that way from birth, and even as teens and adults, can do nothing about it of their own volition. ”
Think about it, if they were helplessly conditioned that way, this would -by means of tradition- imply that the next generations (as long as they live with their parents) are doomed to be “round and sound” as well.
And taking the other direction: How did it all start?This would imply that people were either always fat, or people chose a lifestyle leading to obesity at one point.If they have chosen, then it shouldn’t be impossible to make a different decision now.
by Mr.X
Robert: 68% of your population won’t be suffering from a disease.They suffer from weak will. Maybe, just maybe, grown-up people can start to take responsibility for their own lifes.
Let’s pathalogozise, while we are at it, stupidity, thieving, murdering etc too.How mean to punish these “evil-doers”, they ALL had NOTHING to do with what they’ve done.Believe me.
Btw:Rude? It seems lying is the polite thing to do.
I side with Mr.Lincoln on this one: I call a spade- well- spade.
I’m sure most of these people have put down others, who suffered from something besides the put down, too, at least once in their life.
E.g:
“It is ok to be rascist towards Mexicans or Arabs, but please don’t make any comment about my ‘gravitas’. “
by Tata
Every human is addicted to food, I need a fix of it every single day, several times a day. Sounds like an addiction to me. Is it an eating disorder to choose fattening food over lower calorie food? My obese mother is costing taxpayers tens of thousands in health care, ALL due to illnesses caused by obesity. She ate a gallon of ice cream a day for years, and that was just dessert!
by Christian Gehman
Piss is more important, and more necessary, than food. You can live a month without food, about three days without the other. Geddalife.
by Robert H. Pike
People who suffer from food addiction are suffering from something that started before they could walk and talk, by well meaning parents. Obesity is a profound disease; have a little consideration for those suffering and congratulate the scientists on a possible cure rather than putting down those who suffer.
by melajara
Obviously you are not a (working) poor.
In traditional societies, to be fat or even obese was a mark of power. The slim and slender ones were people barely earning enough to eat their daily calories quota.
Now in our perverse modern society, high carb food or junk food is also the most economical one, so obese people have to be recruited mostly among poor citizens, nolens volens.
This is not simply a question of will, btw, this reminds me of the old saying: primum vivere, deinde philosophari!
by Mr.X
“This is not simply a question of will, btw, this reminds me of the old saying: primum vivere, deinde philosophari!”
You could apply this to yourself.I don’t even need a saying to describe this: We call this denial.I bet you’re fat yourself^^
So, let’s zoom in on your saying: Primum vivere.Well, not all living is “created” equal.Theoretically, you can live a thousand years, doing and thinking the same stuff while doing certain things.You will have less experience than someone who actually tries out things.
About poor fat people- Expertus disco! : I’m from a family of people who are considered poor by the standards of our country.
Nonetheless, when I was young we had aquintances who’d the same income (money from the government, added to their salary to provide a legally granted minimum, that’s how I know) as my family-, and they were twice as large (not in numbers, unless you’re talking weight).Or rather thrice.
They also cconstantly whined about money, despite buying crap in HUGE quantities.Yeah, nutritious food is more expensive…
It is a matter of setting priorities: If you need money to buy fuel in order to drive 300 meters towards a backery, it’s your own fault if you are fat because nothing is left for buying healthy food.
Furthermore, buying less crap means buying in smaller quantities, since satiation can be reached faster.
You’re therefore right, it is not only about will but making smart choices.On average, fat people are dumber.Of course, this is a correlation.Just like fat people are poorer.And smart people tend to achieve more in life.As do people with abundant willpower.You define what you ask from yourself.
“Obviously you are not a (working) poor. ”
Do you imply I don’t work?I don’t call you stupid because of your comment either, so refrain from ad-hominens.Unless, that is, you’re fat and took my comment personally.
“In traditional societies, to be fat or even obese was a mark of power.”
Philosopher: What does traditional mean to you?The rules of modern societies are passed down by tradition, too.What you’re talking about is primitive (in the sence of denotation, not conotation).
Now go eat your tripple-whopper to feel good;)
Ps: I helped enough fat people around me to slim down and gain some muscle.There is no magic in it.Of course, if you need a new I-phone every three months while being rather poor, this isn’t possible.
You guys are just emasculated.
by DeBee Corley
Too easy!
I am craving a lemon pie, so I guess my personal discipline is weak. Darn!
by Ian Clarke
How is Ray’s fat insulin receptor blocking thingummywotsit doing? Wasn’t that in FDA trials a year or two back? The potential number of lives this could save/change would be remarkable.
by Gabriel
That’s the first thing I thought of too — that the mice who had those genes turned off ate alot, never gained weight and lived 20% longer…that’s what he said anyway.
by Ian Clarke
Absolutely. If it works, this would have a huge impact on life expectancy. Not to mention the accompanying social changes re: bullying, depression, inability to work, eating disorders, etc.
Although I dare say those making a living from weight loss programs may be a bit miffed!
by Dwee
Wow, like we don’t already have a cure for obesity. Spend billions pretending the answer isn’t just stop eating when you are no longer hungry, i.e., tell yourself NO. Alas, govment neuromarketers have figured out how very easy it is to buy votes by telling people they are entitled to anything “rich” people have have just because they are people too. Oops, that also makes people fat, lazy and stupid. NO, you are not entitled to anything you want. Learn that, and the fat will melt away. Having to suffer to earn your heart’s desires makes you stronger, wiser and quicker on your feet. Slimmer and sexier too.
by Gorden Russell
Dwee, a lot of hard-working people get laid off. Even those who are still working are getting wages that have been flat since the Reagan Revolution, even though their productivity has soared, greatly enriching their employers. Did you see the news yesterday, Dwee? The Koch brothers bought off the governor, Snyder, of Michigan and he signed the “Right to Work” bill. Now that’s a dishonest euphemism if ever there was one. It would honestly be called the “Right to Work at whatever wages the employer wants to pay” bill. You can look up the numbers in all the newspapers. People in right to work states make from 6 to 8% less than people who live in states with union shops. Even people who aren’t in unions make more in those states. All the wages are higher in those states and the 1% just hates that. It is not anybody’s heart’s desire to apply for food stamps. When you collect “SNAP” you can only afford a lot of rice, beans, pasta, and only the greasiest of hamburger. Yeah, a lot of people do gain weight on a greasy, high-carb diet…even though the food stamps don’t always last into the fourth week of the month and you have to give your children oatmeal for dinner. Some months, they don’t even get that for the last few days of the month. Have you seen the news that food banks are running low on supplies? It is nobody’s heart’s desire to undergo the humiliation of standing in line at the church school gym just to get a box of pasta, a jar of tomato sauce, day-old bread, and expired cans of okra donated by somebody who was cleaning out their kitchen cupboards.
by Dwee
Oh not the evil 1%? You are perfect example of the effectiveness of neuromarketing. It’s well known that Obama hired slew of these psycho pr guys in last months of his election. Beans and rice are CHEAP as dirt and incredibly healthy. Collards and delicious cooked with a meat BONE and cheap and healthy too. POPEYE’s stock is doing quite well because they take food stamps selling grease laden food. You’re just making excuses. The poor are fat because they are encouraged to feel helpless but entitled by politicians who care more about their power than really helping people become stronger, wiser and self sufficient. Sure many people have been laid off, but that’s no excuse to become lazy and fat. The government caused these massive layoffs by making it difficult for businesses to function and thrive. The massive regulations are insane. Wake up!
by Azryan
I really don’t buy this idea of people being on food stamps having to eat garbage. For one, if you can’t afford much food, you ought to inherently be thin -i.e. most of China, Africa and India for billions and billions of examples of this effect. If there was an outbreak of poor Americans staving I would be all for making sure they get fed. But poor fat people is a different matter (not to mention the vast middle class that has no possible excuse).
Also the idea that a carb rich diet is fattening is also a lousy argument. I’m thin, middle-aged and eat carbs every day. I just don’t eat too much every day. Again, see all of the Eastern Hemisphere for a correlation between slimness and plenty of daily rice intake.
You go too far by adding ‘greasy hamburgers’. That’s actually not a cheap thing to get and should not be the choice of anyone on food stamps.
Canned and frozen veggies are affordable, accessible and inexpensive. Getting fat is largely the effect of eating too many calories of any type of food. Rice, veggies, soup, etc…and you’ll get thin poor people.
by Dwee
I was saying people should NOT be able to buy grease laden fast food with food stamps, not that they should. Popeye’s sells fried chicken not hamburgers btw. And rice and beans and collards aren’t garbage. I ate rice and beans at the local health food restaurant today. With (I have no clue what was in it but it was tasty) sauce and chopped tomatoes on top it was yumm.
by Azryan
“expired cans of okra”??
That phrase alone ruined any hope of you being taken seriously. Do you not know how long can food lasts? There has to be vanishingly little that’s expired as it’s handed out. And most donations are not crap people bought but never ate. Most are extra can people buy to toss in the donation box. And they don’t pick out intentionally weird/gross crap to f’ with poor people.
by René Milan
Yeah. The scientist is me. The discovery goes back half a century. The mechanism is to eat less.
by okay
I’m all for science, but then there is the soft science of learning what ingredients are in the items that are being ingested and learning to put the fork down 20 minutes early bc it takes 20 minutes for the brain to know when there is enough in the body.
by Gorden Russell
Those twenty minutes are the toughest temporal paradox, my brain keeps urging me on to eat, even though my belly feels stuffed. I want to start dosing on this enzyme known as tyrosine-protein kinase-2 right away.
by Azryan
I’ve never heard this ’20 minutes’ ‘fact’. If it is a well-tested/accepted fact, we should be telling it to people. But I’ve never heard of it in my life.
I think it makes far more sense either way though to keep teaching people to grasp how many calories they themselves typically burn in a day and what that really looks like in volume of assorted food.
Then again, 99% of fat people know full well they eat too much and too much ‘crap’. They’re not unaware of those facts in the least, so any further education is probably worthless.