Good NYT Article About Genes and Long-Term Weight Gain/Loss
 

http://www.nytimes.com/2007/05/08/he...=5070&emc=eta1

Genes Take Charge, and Diets Fall by the Wayside


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By GINA KOLATA
Published: May 8, 2007

It was 1959. Jules Hirsch, a research physician at Rockefeller University, had gotten curious about weight loss in the obese. He was about to start a simple experiment that would change forever the way scientists think about fat.

Fred R. Conrad/The New York Times

Jules Hirsch, a research physician at Rockefeller University, conducted a simple but groundbreaking experiment on obesity nearly 50 years ago, changing the way scientists think about fat.
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Obese people, he knew, had huge fat cells, stuffed with glistening yellow fat. What happened to those cells when people lost weight, he wondered. Did they shrink or did they go away? He decided to find out.

It seemed straightforward. Dr. Hirsch found eight people who had been fat since childhood or adolescence and who agreed to live at the Rockefeller University Hospital for eight months while scientists would control their diets, make them lose weight and then examine their fat cells.

The study was rigorous and demanding. It began with an agonizing four weeks of a maintenance diet that assessed the subjects’ metabolism and caloric needs. Then the diet began. The only food permitted was a liquid formula providing 600 calories a day, a regimen that guaranteed they would lose weight. Finally, the subjects spent another four weeks on a diet that maintained them at their new weights, 100 pounds lower than their initial weights, on average.

Dr. Hirsch answered his original question — the subjects’ fat cells had shrunk and were now normal in size. And everyone, including Dr. Hirsch, assumed that the subjects would leave the hospital permanently thinner.

That did not happen. Instead, Dr. Hirsch says, “they all regained.” He was horrified. The study subjects certainly wanted to be thin, so what went wrong? Maybe, he thought, they had some deep-seated psychological need to be fat.

So Dr. Hirsch and his colleagues, including Dr. Rudolph L. Leibel, who is now at Columbia University, repeated the experiment and repeated it again. Every time the result was the same. The weight, so painstakingly lost, came right back. But since this was a research study, the investigators were also measuring metabolic changes, psychiatric conditions, body temperature and pulse. And that led them to a surprising conclusion: fat people who lost large amounts of weight might look like someone who was never fat, but they were very different. In fact, by every metabolic measurement, they seemed like people who were starving.

Before the diet began, the fat subjects’ metabolism was normal — the number of calories burned per square meter of body surface was no different from that of people who had never been fat. But when they lost weight, they were burning as much as 24 percent fewer calories per square meter of their surface area than the calories consumed by those who were naturally thin.

The Rockefeller subjects also had a psychiatric syndrome, called semi-starvation neurosis, which had been noticed before in people of normal weight who had been starved. They dreamed of food, they fantasized about food or about breaking their diet. They were anxious and depressed; some had thoughts of suicide. They secreted food in their rooms. And they binged.

The Rockefeller researchers explained their observations in one of their papers: “It is entirely possible that weight reduction, instead of resulting in a normal state for obese patients, results in an abnormal state resembling that of starved nonobese individuals.”

Eventually, more than 50 people lived at the hospital and lost weight, and every one had physical and psychological signs of starvation. There were a very few who did not get fat again, but they made staying thin their life’s work, becoming Weight Watchers lecturers, for example, and, always, counting calories and maintaining themselves in a permanent state of starvation.

“Did those who stayed thin simply have more willpower?” Dr. Hirsch asked. “In a funny way, they did.”

One way to interpret Dr. Hirsch and Dr. Leibel’s studies would be to propose that once a person got fat, the body would adjust, making it hopeless to lose weight and keep it off. The issue was important, because if getting fat was the problem, there might be a solution to the obesity epidemic: convince people that any weight gain was a step toward an irreversible condition that they most definitely did not want to have.

But another group of studies showed that that hypothesis, too, was wrong.

It began with studies that were the inspiration of Dr. Ethan Sims at the University of Vermont, who asked what would happen if thin people who had never had a weight problem deliberately got fat.

His subjects were prisoners at a nearby state prison who volunteered to gain weight. With great difficulty, they succeeded, increasing their weight by 20 percent to 25 percent. But it took them four to six months, eating as much as they could every day. Some consumed 10,000 calories a day, an amount so incredible that it would be hard to believe, were it not for the fact that there were attendants present at each meal who dutifully recorded everything the men ate.

Once the men were fat, their metabolisms increased by 50 percent. They needed more than 2,700 calories per square meter of their body surface to stay fat but needed just 1,800 calories per square meter to maintain their normal weight.

When the study ended, the prisoners had no trouble losing weight. Within months, they were back to normal and effortlessly stayed there.

The implications were clear. There is a reason that fat people cannot stay thin after they diet and that thin people cannot stay fat when they force themselves to gain weight. The body’s metabolism speeds up or slows down to keep weight within a narrow range. Gain weight and the metabolism can as much as double; lose weight and it can slow to half its original speed.
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Research has shown that obesity is largely determined by genetics. What does that say about our obsession with dieting?
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That, of course, was contrary to what every scientist had thought, and Dr. Sims knew it, as did Dr. Hirsch.

The message never really got out to the nation’s dieters, but a few research scientists were intrigued and asked the next question about body weight: Is body weight inherited, or is obesity more of an inadvertent, almost unconscious response to a society where food is cheap, abundant and tempting? An extra 100 calories a day will pile on 10 pounds in a year, public health messages often say. In five years, that is 50 pounds.

The assumption was that environment determined weight, but Dr. Albert Stunkard of the University of Pennsylvania wondered if that was true and, if so, to what extent. It was the early 1980s, long before obesity became what one social scientist called a moral panic, but a time when those questions of nature versus nurture were very much on Dr. Stunkard’s mind.

He found the perfect tool for investigating the nature-nurture question — a Danish registry of adoptees developed to understand whether schizophrenia was inherited. It included meticulous medical records of every Danish adoption between 1927 and 1947, including the names of the adoptees’ biological parents, and the heights and weights of the adoptees, their biological parents and their adoptive parents.

Dr. Stunkard ended up with 540 adults whose average age was 40. They had been adopted when they were very young — 55 percent had been adopted in the first month of life and 90 percent were adopted in the first year of life. His conclusions, published in The New England Journal of Medicine in 1986, were unequivocal. The adoptees were as fat as their biological parents, and how fat they were had no relation to how fat their adoptive parents were.

The scientists summarized it in their paper: “The two major findings of this study were that there was a clear relation between the body-mass index of biologic parents and the weight class of adoptees, suggesting that genetic influences are important determinants of body fatness; and that there was no relation between the body-mass index of adoptive parents and the weight class of adoptees, suggesting that childhood family environment alone has little or no effect.”

In other words, being fat was an inherited condition.

Dr. Stunkard also pointed out the implications: “Current efforts to prevent obesity are directed toward all children (and their parents) almost indiscriminately. Yet if family environment alone has no role in obesity, efforts now directed toward persons with little genetic risk of the disorder could be refocused on the smaller number who are more vulnerable. Such persons can already be identified with some assurance: 80 percent of the offspring of two obese parents become obese, as compared with no more than 14 percent of the offspring of two parents of normal weight.”

A few years later, in 1990, Dr. Stunkard published another study in The New England Journal of Medicine, using another classic method of geneticists: investigating twins. This time, he used the Swedish Twin Registry, studying its 93 pairs of identical twins who were reared apart, 154 pairs of identical twins who were reared together, 218 pairs of fraternal twins who were reared apart, and 208 pairs of fraternal twins who were reared together.

The identical twins had nearly identical body mass indexes, whether they had been reared apart or together. There was more variation in the body mass indexes of the fraternal twins, who, like any siblings, share some, but not all, genes.

The researchers concluded that 70 percent of the variation in peoples’ weights may be accounted for by inheritance, a figure that means that weight is more strongly inherited than nearly any other condition, including mental illness, breast cancer or heart disease.

The results did not mean that people are completely helpless to control their weight, Dr. Stunkard said. But, he said, it did mean that those who tend to be fat will have to constantly battle their genetic inheritance if they want to reach and maintain a significantly lower weight.

The findings also provided evidence for a phenomenon that scientists like Dr. Hirsch and Dr. Leibel were certain was true — each person has a comfortable weight range to which the body gravitates. The range might span 10 or 20 pounds: someone might be able to weigh 120 to 140 pounds without too much effort. Going much above or much below the natural weight range is difficult, however; the body resists by increasing or decreasing the appetite and changing the metabolism to push the weight back to the range it seeks.

The message is so at odds with the popular conception of weight loss — the mantra that all a person has to do is eat less and exercise more — that Dr. Jeffrey Friedman, an obesity researcher at the Rockefeller University, tried to come up with an analogy that would convey what science has found about the powerful biological controls over body weight.

He published it in the journal Science in 2000 and still cites it:

“Those who doubt the power of basic drives, however, might note that although one can hold one’s breath, this conscious act is soon overcome by the compulsion to breathe,” Dr. Friedman wrote. “The feeling of hunger is intense and, if not as potent as the drive to breathe, is probably no less powerful than the drive to drink when one is thirsty. This is the feeling the obese must resist after they have lost a significant amount of weight.”

Intresting article, a little depressing but still intresting...

:)

This is seen in animals as well. In the horse industry we refer to it as "easy keepers." Basically these horses can eat a fraction of what an other horse can eat, with the same activity level yet be quite obese. My horse falls into this category. It sure saves on feed, but I have to resort to putting a grazing muzzle on her to keep her from getting too fat. This muzzle limits her intake of grass to just a few blades at a time. She has never been thin. She always acts hungry and despite tons of exercise, she remains large.

There are other horses at this barn that are fed four times what my horse is. They are on supplements, yet they look almost emaciated. These horses do not act ravenous as mine does despite their boney frame.

I work in biotech and we can genetically engineer mice and rats to be morbidly obese. You simply cannot put these mice and rats on a diet low enough to get them to be thin without compromising their health in other ways.

http://www.pathguy.com/lectures/ob_mouse.gif

I've read of hypothyroidism being brought on by very restrictive weight loss diets (>1000kcal/day deficit) leading to a drastically reduced BMR. Maybe an good endocrinologist could help some of these people keep the weight off.

This also reinforces the recommendation that once someone loses a significant amount of weight (say 10lbs) they should first attempt to maintain that weight for several months before they try to lose more.

This is a good suggestion. If you have a lot of weight to lose, you really do start going nuts being hungry all the time. I know what works for me is to lose 20 lbs, then take a break. I maintain that weight for a few months so I don't feel deprived, then I get up the courage again to lose some more. I can never lose more than 30 lbs at a time, it just takes too long and I wig out.

I wonder what effect age has on this?

When I was 16/17 I went from 295lbs to 220lbs in just about 3 months. I then dropped from 220 to 210ish over the next couple months.

I was 210, give or take from the time I was 17 until I took up racing bicycles at 22. Now I'm 180ish, but it's freaking tough to stay at my race weight of 180 even.

The dropping from 295 to 220 was done on a religious regimen of 1200 kcal per day, running at least 20 miles per week, and spending 3-6 days per week lifting weights for an hour per session of hard body-building focused weights.

Going from 210 to 180...not so much. But, it's hard to stay at 180. If I don't watch it, I'll eat too much, and start to balloon up to 190+. I raced all last season weighing ~197lbs...was riding hard, an awful lot - but I just couldn't keep the food in check, and still ride well. The weight (197 to 180) was taken off running a weekly deficit of 6000 to 10,000 kcal. Not nearly as extreme as before...but the end result is a hard to maintain weight. I have sneaking visions of 170lbs for a climbing race in June, but I don't know if I can suck it up enough to pull that off.

I'm 23, and 6'2 FWIW. Body fat, as per calipers stays around 10 % ... so it would seem that losing this weight is losing muscle, which is fine with me. I'm not a body builder anymore, I'm a bike racer.

I'm sure there's some truth to this, but I really have to wonder - they put fat people on 600 cal/day diets and then are shocked (shocked!) that they behave like starving people? I mean it's just so extreme - plummeting in weight like that is a recipe for rubberbanding. If they lost the same amount over, say, a year or two, I wonder if they'd find the same psychological propensity for falling off the wagon.

My thoughts also. I don't know that the conclusions made are necessarily valid. However, it is a good read and very interesting.

(disclaimer: I may not know what the heck I'm talking about) :D

... Brad

This might make for some interesting reading for the general public, but this sort of thing has been known in the scientific community for many decades. Things like resistin, leptin, GLP-1, and other hormones control weight in such a powerful way that food consumption is almost irrelevent.

Which then begs the question why can't we just modify the way those hormones act, thereby controlling obesity?

Sadly “they” probably can. However, if a drug can’t be delivered orally and produced semi-cheaply the pharmaceutical companies won’t bring it to the mass market. Think of something like HGH, it might be useful for many conditions but because it has to be injected and costs a fortune its practicality is limited.

The study is too extreme. You cannot put someone on a 600 calorie diet and expect them to maintian a low weight. It must be done gradually. It is terribly similar to training. You cannot take a new cyclist and put them on the same training schedule as a ProTour team.
If obesity is so genetic then tell me why the mean European is so much thinner than the mean American. Tell me why I, at 130lbs and 5'9" can sometimes wear a medium pro-cut jersey?

In my opinion, this 'study' was conducted so a scientist could tell fat people it is ok to be fat and there is nothing to be done about it.

This is the worst study that I've ever seen. Put someone on a 600 calorie per day diet and their metabolism automatically switches to hardcore survival mode where it tunes itself to grab hold of every calorie that it can and store it as fat. When they go back to eating a normal diet, as in 2000-2500 Calories per day, they will balloon, because their metabolism is still stuck in survival mode. A person who normally weighs 140 at 5"6' and has for all their life will gain weight like crazy if they're coming off of a starvation diet onto a regular, even healthy, diet.

With all the bad studies and advice out there, it's no wonder that people don't know what to believe and will flock to whatever miracle fad diet there is out there at the moment.

A couple points of clarification:

Modifying hormones can't be done yet because the processes are not clearly defined and other side effects also occur. Considerable work is being done on this subject and I believe progress will be made.

Be careful extrapolating from studies done on "obese" people and taking those conclusions to your own weight loss. One thing we all agree on is the medically obese (by definition, not name calling) people are different than "non-obese" people.

Why has the problem of obesity become epidemic in less than a generation when that is not enough time for any form of natural selection to occur with genetics? The best quote is "genetics loads the gun, the environment pulls the trigger" Some people are set up to be fat, others are not, when everyone is exposed to a diet (typical American diet) that tends to create obesity, only some will succumb.

Finally, we can argue all we want about how people get there, but once you are medically obese, the only treatment effective for more than 5-10% of people is surgery which is 90%+ effect. Current research seems to indicate that bypassing parts of the intestinal tract regulates hormones and a recent conference in Rome showed data that overweight, but not obese, patients with diabetes had their diabetes cured by surgery bypassing parts of the intestinal tract.

Very interesting topic! Snuff, I agree that you will gravitate to a given weight based on your activity level, age, resistance training and diet but at any given set point for these parameters it will take huge moves to change beyond a swing of 10-20 pounds. Just give up on being a climber and take advantage of your power! From what I puruse from these posts you are a fairly sucessful racer, just don't try to win any Alpine stages :)

NYT article does not address genotypeXenvironment interaction issue at all (anybody can get fat if they eat only out of convenience stores and don't get any exercise, and people 'genetically predisposed toward it' can get really fat really quickly).

And, no real discussion of potential qualitative distinction between medically diagnosed obese people vs statistically/epidemiologically obsese (BMI>30).

I think there's a lot of room for discussion of both issues, and am disappointed they don't come up in the article at all. Maybe in her book...

Thanks. That's what the local ex-pro coach tells me too, I just need to stay where I'm at weight wise and focus on TTing and sprinting.

Yet the hills are alluring...

:D

This study makes it sound like some people are just meant to be fat. I wonder whether these people's bodies are just designed for a different type of diet. I'm sure if the scientists messed with the ratio of carbohdyrates, proteins, fats, etc. that were consumed, they might find a diet that works for the overweight group. Maybe they're not genetically disposed to be fat, but are genetically disposed to be fat when consuming a standard, American diet.

Here is my take...
 

Here is my take. As a child I was a complete and utter pig. I ate like crazy for the sheer love of it. At 13 years of age I weighed close to 250# and had a waist line so that no children's clothing would fit me! Finally, I got my act together at age fourteen. I started with what many would call a starvation diet. Breakfast was an apple or something. Lunch, carrots or something, and dinner was normal. Over 3 months, I lost 50 (!!!) pounds.

Of course, being at the weight I was at was still considered unhealthy, but I remained steady at approximately 200#. Four months later, I decided to go even lower. I did every kind of simple excercise I could think of, from crunches, to push-ups, pull-ups, the works. It was a long, Long, LONG 4 months, but I managed to bring myself down to about 170. I remained at that weight for three years.

Then, one summer, I decided to really push the envelope. I did runs (something that is just not easy for me, I have never been good at high-aerobic exercise), walks, swimming, and quite a bit of "starvation dieting" and managed to get myself down to 140. Now, given that I am barely 5'10", this was below my ideal weight level, but I managed to push it even further to one point where I was at 130. I was getting near 100% of my vitamins, minerals and such, but for some reason, I just kept losing. Then I stopped exercising, and just maintained a healthy diet. I am now in "ideal" 150-160# range (I haven't checked in a long while), I can do mild aerobic exercise, I can bike 50k a day, and I can eat a fair amount without gaining any (significant) weight.

So, what happened?

I have no scientific background, but I'd have to say I eased my body into it. It definitely went into starvation mode, but when I ballooned back from the 130-140, it seemed to be quite content at the 150-160 level and had no desire to return to my previous weight.

However, I can't say genetics had much to do with it. Both sides of my family aren't known for having "healthy" bodies, and all are overweight to a fair extent. So I have a hard time swallowing the "its genetics pill". Saying that removes a lot (not all) of the responsibility and allows the obese individual to simply give up and say "c'est la vie!".

And to those who might be curious, I doubt I am some fluke. My mom asked me to help her lose weight, and I followed a similar (though less extreme) regime with her, and her body lost a solid 20# and she has kept it off, not through anything excessive, but simply not by over eating.

From my point of view, it is a choice. Fat people can become thin, thin people fat.

I was the same way.... I got up to 235 at age 17 (6' tall, medium build) before getting fed up with being fat. Obesity runs in my mom's side of the family... so maybe genetics did play a role, but mostly I just ate like crap. I bascially starved myself like you and lost 75lbs within a year. At that point, I weighed 160, which really is my ideal weight. However, I had lots of loose skin and I still thought I looked fat, and I think I developed sort of a mental complex about weight loss, perhaps some mild anorexia. I continued to lose weight through light eating until getting down to 135lbs, which I maintained until I was 26. At that point, I got in a motorcycle accident and my weight plummeted to 119 lbs. My doctor put me on antidepressants and threatened to feed me through a tube - so I reluctantly ate lots of food and gained weight. I held steady at 150 for a couple of years, then my metabolism began slowing, probably due to age, and my weight crept up to 175. I started cycling a lot last year and lifting weights and I'm now holding steady at 160.

I stick out like a sore thumb at family gatherings because I am at the correct weight.

I think that genetics plays a role in predisposing people for weight gain, but in the end, it's up to everyone what weight they want to be.

I think there is another factor at play now that I think about it. There are tonnes of diets on the market. There is the LA diet, the Atkins (yuk!) diet, the this diet, the that diet, the I'm-pulling-this-out-of-my-ass-and-reaping-huge-profits diet. But they are ultimately just diets. Yes, if you starve yourself, you will loose weight, guaranteed. But you have several things going against you:

First and foremost, most people who diet, exclusively diet and perform little, if any serious exercise. Your body, I believe, interprets this as a scarcity of food mode, and aims to store as much energy as possible in case the food disappears altogether. It is a simple survival strategy.

However, the second food becomes readily available, your weight will balloon because your body is still in ultra-conserve mode. Think about it, lets say I am a starving animal, and I happen across a pile of food. Well, that ain't normal, but what the hell, my body says, take what you can get, because this is a once-in-a-life-time opportunity. But it isn't. Because this animal now has a ready supply of food , but the body is still wary and wants to store everything it can. Same with dieters. You starve the body, the body then goes into dormancy until food is available, and then leaps into action conserving everything it can.

Now, alternatively, you have those like myself who dieted and exercised. And not just a few minutes a day, or a few push-ups. At my peak of exercising, I was doing 100 push ups, 200 sit ups (not crunches!), 50-75 chin ups, and I could run 4 miles in 12 minutes -- and I did! So my body said, whoa! There must be a reason he is doing this, and therefore it adjusts the metabolism to work with this new environment. The body raises the metabolism, and so long as it gets a low, but sufficient calorie count, it continues to operate. When I stop exercising as much, my body slows down and the metabolism drops, but to levels nowhere near where I was previously.

And I will re-iterate, while genetics probably plays a factor, I think lifestyle plays a far, Far, FAR more important factor! Get yer lardy ass off the couch and get walking. Everyday I try and get 3 hours of walking, and one hour of biking in, minimum! (Granted, I do wake up at around 3 am.... but hey, I gotta do what I gotta do.... he says as he mumbles off to bed to collapse).

Sure...

I understand the desire to simplify things and the impression that what worked/happened for you is the way it is for everyone. However, anectdotes can't always be applied to everyone else.

The debate between genes and environment is an old one and applies to many issues besides weight including psychologic issues, learning behavior, etc.

No doubt we are scraping the surface of a complex interaction of many factors that play out to different degrees in different people with both genetic and environmental components.

What we can all agree on is daily, at least moderately strenuous exercise is crucial to good health and weight maintenance and that cycling is an excellent choice in that regard.

All right.... it was 6 minutes, but let me add dramatic effect darn it!

Damnit Jim, I'm a anecdote-teller, not a freakin' encyclopedia :D

Oh, please don't mistake my post as saying (however, now that I re-read it, I can understand it coming out that way) that EVERYONE'S body would work just like mine. I think everyone would agree that is simply not the case (and let me tell you, with some of the weird stomach problems I have had in my life, bless yourself! :D)

However, I think that, at least in recent years, there has been a SIGNIFICANT trend of buck-passing in our society.

"Oh no, I can't lose weight, I can't diet! My genes would just make me fat again!" (/end sarcasm)

And let's face it, not everyone is going to just fall down more than a hundred pounds! There are lots of people that are probably healthier than me who happen to have beer guts. In fact, I have heard more than one study proclaim that having a bit o' meat on your bones will ultimately give you a healthier life than Mr. Skin-and-bones.

And then there are people who, for definitely medical problems, are obese or even morbidly obese. These people require theraphy (of the chemical kind) and surgery to reverse these effects. Many of these people again go on to live happy, healthy lives without ever needing to kill themselves with exercise.

But, I would wager there is at least a third, if not more of the population who simply don't REALLY WANT to lose weight. They want to look good in a bikini, or to have a six-pack, but they aren't doing it to make themselves happy, and therefore it doesn't stick.

Of course, this is just my 2c, and given the rate of inflation, I think it means less than it used to ;-)

He's half horse, leave him alone.