Mice Given an Experimental Gene Therapy Don't Get Fat (boingboing.net)

AmiMoJo shares a report from Boing Boing: Researchers at Flinders University knocked out a gene known as RCAN1 in mice, hypothesizing that this would increase "non-shivering thermogenesis," which "expends calories as heat rather than storing them as fat" -- the mice were fed a high-calorie diet and did not gain weight. In particular, the modified mice did not store fat around their middles -- a phenomenon associated with many health risks, including cardiac problems -- and their resting muscles burned more calories.

[Vice News reports:] The study's authors point out that there's a time and place for RCAN1's role in preventing calories from being burned: namely, back when food was scarce and calories weren't so readily available. In the modern world of "caloric abundance," however, too much fat is being stored and real health problems are ensuing as a result. The researchers suggest that "These adaptive avenues of energy expenditure [such as RCAN1] may now contribute to the growing epidemic of obesity." "We looked at a variety of different diets with various time spans from eight weeks up to six months," said Damien, "and in every case we saw health improvements in the absence of the RCAN1 gene. "Mice on a high-fat diet that lacked this gene gained no weight."

Comments

Wrong way

[religionofpeas]

Trying to get the body to burn more calories is the wrong way to solve the obesity problem. People need to figure out ways to ingest less calories, not burn more. Eating less saves money and time you would otherwise need for food and eating. Also, increasing metabolism most likely has bad side effects on longer term, such as higher rates of cancer due to increased oxidative stress.

Of course, it's hard to make a profit on people eating less.

Re:Wrong way

[AmiMoJo]

It's not ideal for long term use, but as a way to lose weight it's very promising.

The reason why fat people find it so hard to lose weight and keep it off is that the body fights them. When they cut down their calorie intake it goes into starvation mode. They feel tried all the time and it reduces burn to a minimum, which ends up meaning they need to diet extremely aggressively to get anywhere and will likely be unable to keep the weight off. 1500 calories/day is neither healthy nor sustainable, but in starvation mode that's what they need to achieve.

This gene seems to fix that. Say it could be turned on and off at will, or perhaps turned off but then the body regulated with medication instead. People could maintain a healthy 2500 calories/day diet with all the nutrition they need, and still lose weight and then maintain at that level.

Re:Wrong way

[Kjella]

Trying to get the body to burn more calories is the wrong way to solve the obesity problem. People need to figure out ways to ingest less calories, not burn more.

It's certainly one solution, but it's a bit like saying the only right way to avoid STDs and unwanted pregnancies is abstinence. I love eating food, like sex I know it's just evolution hard-wiring survival and reproduction into my pleasure centers but nothing is going to stop me wanting to dig into a juicy steak. It's the flavors, texture and smell that makes me want it, the calorie intake is just one tiny bit though I suppose you couldn't get the sugar rush without actually consuming the sugar but I wouldn't mind something like a "condom" for my stomach that sent the calories straight through. Or sent my metabolism into hyperactive like I was running for miles to work it off, burning it away.

Eating less saves money and time you would otherwise need for food and eating. Also, increasing metabolism most likely has bad side effects on longer term, such as higher rates of cancer due to increased oxidative stress.

I doubt that, athletes that during their career have eaten and spent way more calories than average don't seem to suffer any ill effects. Sure, it would probably be a really bad idea to change it permanently if you ever got lost and had to live off very few calories in an emergency. And it certainly could be hard to get off the mental addiction that you can just gorge on anything without getting fat if you lost access to the calorie blockers. From an environmental perspective it's a waste. But from a personal perspective I'd like to eat my cake and have my waistline too. There's no doubt that I'm overweight and my health would be substantially improved if I was thinner, but dieting sucks. It certainly works, but it's always going to suck.

Re:Wrong way

[AmiMoJo]

Here's an interesting study: https://www.ncbi.nlm.nih.gov/p...

A more readable write-up here: https://www.scientificamerican...

TL;DR the people studied lost weight but ended up in an unsustainable position, and put a lot of it back on. Not to mention the other health problems they suffered as a result.

Re:Wrong way

[Megol]

Reduce intake to somewhat below that required to maintain current body weight and then start exercising to burn more. No starvation mode, more calories are used to build muscle. Gradually step down intake as the stomach get accustomed to less food, step up exercise as the body get accustomed to being used for what it was evolved for. But it isn't a quick fix - which is what most people want.

Re:Wrong way

[dfghjk]

What is "starvation mode"? It's clear you don't know the answer.

"Most people fail at losing weight because of lack of discipline."

Ah yes, the old "obesity is a character issue" argument. In other words, I've never been fat so you're fat because you're not as good as me.

Try educating yourself. Obesity is a condition where the body believes it needs to gain weight despite having adequate energy reserves. By definition, the body operates at some level in "starvation mode".

Re:Wrong way

[dfghjk]

"People need to figure out ways to ingest less calories..."

Exactly what this is targeting, despite your inability to understand it. People are not fat because of the desire to consume more, they desire to consume more because something is wrong.

One of the oldest, tired-est cliches among the pretend intelligencia here is "correlation is not causation". Well, eating more certainly correlates with obesity but "correlation is not causation". I find it interesting how no one here ever seems to get that when it comes to weight management. Could it be that they've never experienced it themselves?

The solution to obesity is understanding and addressing causation, not correlation. Eating less is already known as ineffective except to those who lack experience. A treatment that solved the underlying cause would result in less consumption, not more.

Re:Wrong way

[Hognoxious]

That's bullshit, you don't have to go into starvation mode to lose weight.

You totally failed to understand what he wrote.

Re:Wrong way

[Actually, I do RTFA]

That's pretty dumb. Some people can eat whatever they want and stay skinny. Some people have to work really hard. As long as being thin is an advantage, I see no reason to work hard to get it.

If there were a gene that made you smarter, would you write something like "you should just read more books"?

Re:Wrong way

[AmiMoJo]

If it really was that simple we wouldn't have the problems we have with obesity.

We could argue about where the problem lies, but it's pointless. Even if it is just people with no willpower and too lazy, how does knowing that help? We have tried shaming and berating, it doesn't work.

What does work is surgery, but that's drastic. This looks like a good option.

Re: Wrong way

[Anonymous Coward]

Why do you care if someone else exercises? If fat can be kept off the body without exercise, why is that a bad thing?

Re: Wrong way

[Anonymous Coward]

You are not wrong, but the fix is not to say "so stop doing that" as clearly many cannot. Also, with gene's playing a part in whether fat accumulates or not... perhaps some people have a stronger propensity towards accumulation than others. If that is the case, it is also a medical condition. You COULD eat less and exercise 3 hours a day... just like someone on dialysis can be hooked up to a machine for hours each day. But we seek to heal these issues.

Re:Wrong way

[WhiplashII]

You are obviously under 30.

When you get to be 40, see of you still believe that.

In my case, I lost the ability to walk or perform almost any exercise for 20 years (ages 19-41). I gained a moderate amount of weight, but nearly constant dieting kept me below 290 lbs. Then I finally had a doctor that fixed what was wrong with me, and I started exercising. (My first exercise: slow the rate of fall as you slide down a wall, I kid you not)

Upon exercising (and being 40), I gained weight. I only eat 1 time a day, just to maintain. I work out heavily (extremely motivated!), and am constantly exercising.

My point: not everyone is like you, so stop acting like a butt.

Re:Wrong way

[alvinrod]

Way back in the day Michelin was looking to increase sales and one way to do that was to get people to buy cars and drive more (hence more tires sold) and they needed a reason for people to want a car. So Michelin started reviewing restaurants (awarding them Michelin stars which are still given out today and considered somewhat prestigious) with the thinking that people would want to buy a car or use it more if they could have an exceptional dining experience.

Re:Wrong way

[jdschulteis]

If a useful treatment for obesity ever arises from this research, my money would be on a drug that suppresses the activity of this gene, rather than genetic engineering.

Re:Wrong way

[AmiMoJo]

I think it's worth explaining about starvation mode. It's not a medical term, it's the popular name for what happens when you reduce calorie intake. The body reacts by conserving energy, reducing the amount of energy it burns at rest, i.e. the amount it would use if you did nothing all day. This is accompanied by feeling tired and hungry.

This study and article about the study are very enlightening:
https://www.ncbi.nlm.nih.gov/p...
https://www.scientificamerican...

As you can see the test group went from an average resting calorie burn of 2600/day to 1900/day. So a loss of 700 calories/day burned, or about 1.2 hours of vigorous exercise like fast cycling or jogging, before it even starts to have an effect on their weight.

And of course, they feel tried all the time and being obese have to be careful about not injuring themselves during exercise (jogging is probably a bad idea), and have to carefully plan meals. Few people have the time to do this, especially when they have to work and need to be reasonably awake to do so.

This is why the "just eat less, do some exercise" advice doesn't work.

Re:Wrong way

[LostMyAccount]

There has never been a fat person who did not shed massive weight when reduced intake is combined with real physical activity.

Go read Gary Taubes' book "Why we get fat". He has an entire section of the book that covers individual and population studies of people who did demanding physical labor and gained weight, everything from oil field workers to a group sedentary people who trained for and ran a marathon and dropped only an average of about 5 pounds. This is the larger problem with the obesity debate. So much emphasis is on calorie reduction, exercise and the inevitable character critique that comes from berating "lazy fat people" who can't lose weight and keep eating".

There's almost no emphasis on the nature of the calories consumed and their relationship to the body's metabolic processes of lipogenesis. We've known that insulin controls lipogenesis and what causes insulin production, yet we're still talking about only in terms of calories eaten.

I actually gave very low carb eating a try, and in about six months I'd dropped about 20-odd pounds without any exercising and without any calorie/intake regulation. I simply ate low carb foods when I was hungry. Say what you will, but it worked and I'm fairly convinced Taubes and low-carb are onto something.

What's kind of interesting and telling are the substantial number of people who are militantly opposed to anti-obesity strategies that don't involve caloric restriction and regimented exercise. It's like a religion. If they invented a cheap and safe pill that let people cut their weight without doing anything I'm convinced the diet-and-exercise crowd would still oppose it. Why? Most of diet-and-exercise is just moralizing. I'm sure we'd see arguments like "the anti-fat pill is bad for the environment because people are creating too much trash and sewage with their overconsumption." The responses are akin to telling a Catholic you can get into heaven without believing or praying to God.

Re:Wrong way

[davemchine]

Every time there is an article on weight someone comes in and says, "people just need to eat less." When you get older you will learn more. Some people are just "fat" and there's nothing they can do about it. My wife and I eat the same meals every day. She is skinny and healthy while I am obese. Same meals. It is NOT always a matter of counting calories. I have two daughters. One can eat a gallon of ice cream every day and she is medically underweight. The other only eats twice a day like a bird and is obese. Science will figure it out eventually but it isn't as simple as people would like to think it is.

Re:Wrong way

[RhettLivingston]

I am in full agreement that this approach is the wrong way to solve the problem, but believe that science needs to figure out ways to allow people to ingest less calories, not the "people" in general.

If a medicinal regimen was so hard to stick to that less than 10% managed to do so, the FDA wouldn't even consider approving it. They routinely deny approval in those situations. The same should apply to doctor's advice. No doctor should be able to prescribe a course of therapy doomed to failure in most situations and set people up to be lambasted for not succeeding in a battle that most don't succeed in. Those that do likely have genetic or epigenetic adaptations that allow it.

For example, I know people who seem to get their chemical satisfaction fix from successfully exercising their will to do something really hard and that fix lasts for the long haul. They are the ones who never say it is easy but smile all the time when they are talking about the struggle as if there is something arousing about it. They are credited with having willpower, and the rest of us are encouraged to follow their example as if those of us who don't have the advantage of the same reward system have the same chance at success. Poppycock. If we're really lucky, some trauma may push us into an epigenetic change to get that ability, but otherwise, no chance.

Finding a way to effect the same changes this gene does would set us on a course to increasing our calorie burn for no productivity gain. We would likely adapt to consume even more calories and need further changes to burn even hotter. It would spiral, increasing our consumption at a time when the world really needs to be reducing consumption.

Instead, we need to continue looking for the genetic or epigenetic keys that drive the desires. It would be awesome if we could find ways to break the reward system that the body has in place for sugar intake. But we must be careful - I have seen the results of anorexia which is just the result of a system of rewards for not eating being activated - likely at an epigenetically reinforced level in many of those that have it persistently.

We might also find ways to get sugar intake to more reliably trigger the satiation response at low levels.

I am one who does not get a full feeling from being physically stuffed. It seems to only come from a consumption of fat. So, when I get on a carb and/or sugar kick, I can eat huge quantities and never feel satiated even when in pain from being physically stuffed. When I go back to a very low carb diet I feel satiated with much less and also feel much more energetic. I perceive that as two problems. First, there is a carb reward that causes me to break out of the diet that makes me skinny and energetic and I'd love to have that reward system changed. Second, I don't have a satiation response to carbs of any type. Fixing that could reinforce or replace a fix to the first problem. Neither of these changes would increase my usage of resources.

Re:Wrong way

[Solandri]

The problem with reducing intake is that our bodies are not wired for the small number of calories needed to live a modern lifestyle. About 15-20 years ago, PBS ran a reality show called Frontier House, where they put volunteers in a situation a typical pioneer would've faced in the late 1800s. They had to raise and harvest sufficient crops and livestock during the summer to hypothetically feed them through a winter. Halfway through, the volunteers demanded to see doctors because they were eating 5000+ calories a day heavily loaded with butter and fat, yet they were still losing weight. Something had to be wrong with their bodies. The doctors examined them, and pronounced them fit as a horse.

It turns out that without machines to do all the heavy lifting for you, you needed to eat that much just to survive back then. And it wasn't just the men working the fields who were burning prodigious amounts of calories. This extended to the women too - no washing machine, no dishwasher, no vacuum cleaner, no blender, no prepackaged meals. You had to do all those cleaning tasks by hand, make all your meals from scratch. The women remarked that as soon as they finished cleaning up after one meal, it was time to start preparing the next meal.

Even estimates for the diets of slaves (who were not the best-fed people) put their daily caloric intake between 3000-8000 calories/day (towards the high end during harvest season). So the problem isn't that we're eating too much and we just need to eat less. We've already substantially reduced our food intake from the historical levels that our bodies are wired for. The problem is that our physical activity has decreased much more than our appetites have.

Could be useful if they learn more.

[AbRASiON]

I'm sure some here will say "this sounds unnatural and all people need is discpline" and you know, a speech like that is correct.

Life is also too damn short and some of us genuinely do have a pretty poor metabolism, or in my case I've now gained and lost weight so many times, I have the excess fat cells in me, which is hard to get rid of (read up on it, fat cells get bigger and small for you, unless you REALLY push too far, THEN they multiply)

If you said to me "you can take this drug, with 0 current side effects, but you'll live 2 years shorter" I'd take it.
Heck, hypothetically if they made another one for free time "you can take this drug, sleep 3 hours a night and feel totally and utterly normal and well rested, but you lose 5 more years" I'd take that too.

A good thing?

[LostMyBeaver]

Somehow, I am reminded of a scene from Catching Fire where Suzanne Collins introduces a modern misinterpretation of the word vomitorium. It was believed at some point that the Romans would overindulge in food and visit a room dedicated to vomiting to avoid the negative effects and be able to eat even more. (This is not what the word means, but I suppose it makes good TV).

Obesity is associated with many illnesses, ailments and diseases. But obesity is also a symptom. I would hazard a guess that people who do not move enough to burn the calories they consume will still be prone to most of these problems whether they store excess calories or not.

The associated issues with this are numerous. If we provide gene therapy that would discontinue storing excess calories, it would allow more people to overindulge. That would increase consumption and place an additional burden on the supply chain and the natural resources of the planet overall.

People would live longer while burdening society. Obesity is one of the few remaining tools nature has of balancing itself.

Consider stupid other things. If you consume more (and we will) and your body lacks the facilities to store it in quantity, it will be ejected more often. This means that we will use toilets more.

What will be the added cost of fresh water consumption and toilet paper usage? Using a bidet could alleviate portions of the paper related issues, but unless it were supplied by recycled water, the environmental impact of the additional water consumption would be outrageous and likely untenable.

I am quite sure this is a very very bad thing.

Brain surgery.

[dddux]

I don't think gene therapy is the right solution, especially because it doesn't address the main problem: people eat too much shitty food. Too much of something I don't even call "food". I'm of reasonable weight for my age, but I can thank that only to my lifestyle: no sweets, no fast food, no snacks, no sandwiches. Just normal food made from fresh vegetables and ingredients bought at the farmer's market, 3 times a day. No special diet will ever solve the obesity problem because people can't stick to any of those diets and make it a lifestyle. So I'm a proponent of brain surgery. Just remove the part of the brain that is responsible for craving sweets, snacks, pastry, hot-dogs... fast food in general, and you remove the obesity problem. Kinda half-joking, of course. But it's the only solution to make people eat a sensible and healthy, sustainable diet, and make it a lifestyle.

Re:Brain surgery.

[Actually, I do RTFA]

Surely you are aware that many people can afford neither the time nor the money to have "three meals a day from fresh vegetables they pick up in the farmer's market", right?

Re:Brain surgery.

[hey!]

The obvious counterargument to the notion that obesity is a person's genetic destiny is that 50 years ago, people were much less fat. 75 years ago we were slimmer still.

Unless there has been incredibly rapid natural selection for fatter genes on a massive scale, the difference has to be environmental. That's the food we eat, how and when we eat it, and the activities which burn calories. And if you look at the differences in the way people live, it's a perfect storm. People move much less -- even when controlling for how sedentary their occupations are; and they live in an environment where there is continual access to food that has been engineered to be quick and convenient to consume almost mindlessly. Honestly if it were just sandwiches, I think we'd be OK, but so much food today is designed to be psychologically rewarding but not sating. The Cheet-O is the perfect food commodity: eat one and you'll want another, and you will never feel like you've had enough, much less too much.

Genetics plays a role, sure; but the majority of healthy people will put on weight in the kind of environment we've created for ourselves. Increasingly it's the genetic outliers who don't do that.

Our attitudes toward things like hunger haven't helped. We've been trained to view ordinary hunger in an otherwise well-nourished person as a crisis to be avoided at all costs. Many doctors advise their patients to avoid it all costs by continually feeding themselves small meals. That can work, but it's extremely challenging to balance energy input and output.

If you've ever tried fasting, that all seems kind of ridiculous. You don't need food every couple of hours, you can go days without food with no harmful effects at all. Learning to treat hunger as a normal, non-urgent situation is a big part in learning not to overeat in a food-saturated world. Once you've done it a few times, you realize a hunger pang isn't an emergency alarm. It's a routine reminder to think about getting some food, one that turns off in a few minutes and can be safely ignored for a few hours or even days in a world where food is nearly always at arms reach.

comfort and stress - Re:A good thing?

[AmusingClown]

I was thinking the same thing as parent re: "would increase consumption and place an additional burden on the supply chain and the natural resources of the planet overall."
That would apply to the shorter term. Now look longer, when civilization falls, and we need conserve calories again and can't (we'd gamble on some natural selection recreating that gene effect in order to come out the other side still a species...)

The other thought I had was regarding a big root cause - habitual overeating for comfort. I wonder if knocking out this gene would have any effect on that mechanism? or if lack of calorie storage would be noticed by internal systems and trigger some other unpredictable behavior influence?

I'm Fat!

[gerald.edward.butler]

I'm 49 years old. I was incredibly skinny all my life (like skin and bones) until I was about 30. I had severe asthma as a kid and we were relatively poor and didn't always have enough to eat. Also, my metabolism was high. I never exercised that much due to asthma, but, I was always unhealthily skinny. I even had "low cholesterol" to the point they recommended I eat more bacon. When I joined the Army, I was 5'10" and 118lbs soaking wet. The drill sergeants made me eat double meals to put on weight in Basic and AIT. By the end of that (about 60 weeks in total), I was up to about 130lbs. I stayed that way the entire 5 years I was in the Army and left the Army at 23 weighing about 140lbs soaking wet.

Why am I fat now? Simple, because I sit 10 to 14 hours per day working and end up stress-eating more than I should. Not a ridiculous amount, but, it adds up. Day after day, week after week, year after year. I started putting on weight around 30 and I'm now at 290lbs. Almost all of it around the middle. Is it genes? Is it the food industry? Nope. Not really.

It's sitting and not getting enough exercise and continuing to eat like I were getting exercise (and stress to a lesser degree). It is my responsibility to take charge of my life and do something different. In this case, that means I have to get more exercise, sit less, and watch what I eat a little more carefully. I've been doing that now and I'm starting to lose weight.

It really is as simple as that. Stop looking for simple solutions that don't require any effort. Effort is good. Pain is good (it let's you know you're alive). You don't always have to feel good (drug addicts take note). Sometimes, when you feel like shit, you just have to soldier up and drive on.

Re:I'm Fat!

[RuiFRibeiro]

It is not only being inactive. It is what you put in your mouth. It also depends on the quality of food, how many times you are eating, and also into what you are drinking. It also depends on the dietary habits of you other half.
I am about the same age. I was feeling very sick when 30 doing to weight and shed all that weight with a very aggressive diet.
Case in point, drinking only water, avoiding bread, cheese and milk, and sweets, and maybe even coffee helps your body process better the food. Also portions matter, your beef should about the size of your closed fist in size.
Returning to the quality of foods avoid frozen, processed and ready meals goes a long way too.

Not so much

[rsilvergun]

a huge part of what leads to obesity is gut bacteria. Genetics also plays a role. As has been pointed out elsewhere on the forum a lot of us fatties do so because we need to keep our energy levels up. In America you work 40-50/hr /week minimum like it or not. 6 hours into an 8 hour shift there's still work to do, and you need to be alert enough to do it. Then it's time to go home, cook for the kids, help with homework (because we've cut funding to schools for 40 years straight now so it's not like the teachers are gonna do it), clean the house up and try to get some sleep so you can do it all over again.

You are clueless man

[lamer01]

See my post above. Yes you can maintain a healthier weight and not be fat if you really expend tremendous amount of energy fighting your innate genetic predisposition. I've lived long enough to have seen people who can ingest many thousands of calories and not gain any fat and others who have to be very diligent about their lifestyle so that their body doesn't balloon up with fat. It's the genetic lottery and we all accept it but why does it need to be that way? Why do we need to accept that some of us have to fight really hard to have a healthy weight and other can get that feature for free? Science says it's a single gene. Obviously some people have it and other don't. Why do you think we cannot per-empt nature and improve this situation?