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Obesity and Genetics

Yesterday I ran across a nice article in the New York Times, which is an excerpt from Gina Kolata's new book, Rethinking Thin. I'd heard the odd reference to fifty-year-old research from Jules Hirsch, a physician at Rockefeller University, that strongly correlated (70 percent—strong!) obesity with genetic heritage. The article goes into some detail about that research (and much else) and is worth reading, and I may buy the book.

As I've said many times in this space, we know far less about the workings of the human body than we claim to, and the stronger the conventional wisdom about one health condition or another, the less the scientific process seems to hold any authority. Perhaps the strongest conventional wisdom about obesity is that it's all your fault, and if you would just stop being such a glutton or maybe walked around the block once in a while, you'd lose weight.

Like almost everything else in biology, it is hugely more complex than that. Let me recap what I've learned in my 54 years. (My long-time readers have read some of this before.)

Age matters—in some people more than others. The woman who picked up my responsibilities when I left Xerox in 1985 told me that when she was 41 or 42, she "blew up like a balloon." (Her own words.) She didn't change her diet at all, but in the space of a couple of years, she put on over fifty pounds. Nothing bad happened in that time; she didn't get divorced, or lose her job, or a parent, or any other loved one. She was a sweet person who lived simply and sanely, but as she entered middle age she just gained weight quickly and irreversibly. I had lunch with her many times in our last year as co-workers, and she ate almost nothing compared to what I ate.

Diet matters—in some people more than others. I gained twelve pounds very quickly after I got married, simply because I started eating regular meals. As a bachelor I lived on Golden Grahams cereal and not much else; eating alone was boring and I walked all day at work with a toolbag in one hand and a vacuum cleaner in the other. Once I began eating sane meals as Carol's spouse, I gained weight but felt better. I gained a little more weight (about fifteen pounds) in my mid-forties, but I'm pretty sure now that it had less to do with age than with my body's reaction to sugar, particularly the high-fructose corn syrup in all the iced tea and Mountain Dew that I was downing daily in the land of single-digit humidity. (I know, it was all the wrong stuff to drink. I don't make that mistake now.) Once I mostly eliminated sugar from my diet, I lost fifteen pounds in almost no time at all. I think the body handles sugar better when you're young, and a good deal of that may be a matter of insulin resistance. The first thing anyone should do in an attempt to lose weight is knock out sugar. It's not as hard as it sounds and I know numerous people whose reactions were like my own. On the other hand, I have friends who claim that sugar has no effect on their weight, and that what makes them gain weight is fat. I'm suspicious, but I'm also an empiricist. What works, works, and it's our job to do the science and figure out how and why.

Exercise matters, though in subtle ways and maybe less than we think. I didn't gain any weight at all when I went from a vigorous walking job to a desk job in 1977. I began walking regularly in my late thirties, not so much to lose weight but to dissipate job stress and feel better. I didn't lose weight when I began walking. When I get sick and stop walking, I don't gain weight. On the other hand, once I began a weekly weight-training regimen, I put on significant muscle mass. Muscle burns calories 24/7, and since I gained muscle, my weight has drifted downward. Most of the lost weight came out of my gut, which from a health standpoint is the worst place for men to have it.

So. Do genetics matter? Over the years, I've become increasingly convinced that they do, based on observations in my own family and circle of friends, and in articles I've read. I'm convinced that there is a "fat gene" and (more to the point) an inherited weight value that the body likes to maintain if it can. (For me, that value is about 155.) Fat people can get thin if they reduce themselves to a starvation diet (see the Times article referenced earlier) but as soon as they begin eating normally, the weight comes right back on. Further research I've recently found (courtesy Frank Glover) indicates that there is definitely a "fat gene" in mice, and chemicals have been discovered that seem to override the fat gene's regulation of mouse metabolism, which then burns calories more quickly.

Sugar—of which there are several different kinds—is a wild card. I don't think we completely understand how sugar affects human metabolism, and we desperately need more research. Sleep may also be a wild card; a Mayo Clinic seminar we attended once presented some research suggesting that sleep deprivation both raises your blood pressure and increases your weight. I intuit that the "freshman fifteen" effect may happen because college kids studdenly stop getting a full night's sleep. Ditto women with newborns who complain of not losing their pregnancy weight—getting only three good hours of sleep a night may be an issue. We certainly need more good science here.

The conclusion I come to is that weight is, at the bottom of it all, about metabolism. If we turn metabolism up, we lose weight. Genes appear to regulate the body's metabolism within certain bounds, and although we can tweak metabolism by tweaking diet, exercise, and muscle/fat ratios, metabolism dictates whether we are thin or fat, given enough food to not feel ravenous all the time.

But what we really need to do is stop assuming that we know more than we do—and we really really need to stop assuming that fat people are all lazy gluttons.

Comments

(Anonymous)

genes...

In my own case, I know that my mother's side of the family leans toward trim, while my father's side has been more on the heavy side. For my part, I can get trim and stay so only through some fairly serious exercise. By that I mean 4-5 days a week, and 1 hour+ per day, half of which is cardio.

Diet ought to make a big difference, as I am hypoglycemic, but unless I take fairly drastic steps, it does not. I can subsist on salads, and not lose weight. In more ordinary eating, I curse the diet fad folks who continue to purge fat from our food -- fat tells the pancreas to stop producing insulin, so it is a tool for me.

I'm currently overdue to dive into serious exercise, and my weight now is similar to my father's weight 40 years ago. The good news is that I know from experience that it will do the trick. The bad news is that in this climate, I will battle heat, humidity and pollen, as well as fat.

Bill Meyer

Obesity and genetics

A blessing upon your head.

I suspect that as human understanding of human biology continues to advance, we'll discover that *gasp* all metabolisms aren't created equal, and they don't stay the same as one ages. The former is obvious. Some people are insulin resistant, and do much better on a protein and fat heavy diet. Other people get gout on diets like that. Also, Most peoples of the world are lactose intolerant after childhood.

As for metabolism changing with age, one need only go back to your previous post about vitamin B12 and the torturous chemical process by which it's digested, and how that breaks down with age. I tried B12. It seems to help.

The one biggest thing one learns when one sees a display like Body Worlds is that human bodies are not mass produced. They're variations on a theme, physically and structurally. Yes, we're all very similar, but our science is reaching the point where to understand how our bodies work, we must begin to contemplate them as individual organisms.

On a larger view, I have to wonder if we're reaching the limits of reductionist science generally: if perhaps it's time to reevaluate the scientific meme of reduce, experiment, generalize, and consider that above a certain resolution, generalization is no longer possible.

-Jim

Scientific process and weight

There are two problems with the scientific process, and neither of them are new.

First, unless you have a theory to prove or disprove, the process doesn't work. The story of Dr. Jenner, who demonstrated that cow pox was a vaccine against smallpox, is as good as any. He couldn't explain why it worked, so it was not generally accepted.

Second, scientists are people too. The example here is "luminiferous ether." Up until the early 1900s, scientists thought that light, which is a wave, had to be transmitted in something. That something had to be a magical substance, with no weight or mass. Then this Swiss patent clerk (you may have heard of him - guy named Einstein) came in and said "well, duh, light is a wave AND a particle." This was not terribly popular, and wasn't accepted by mainstream science until the 1920s - when the old fogies had retired.

My theory (or actually, the one I stole from the South Beach Diet guy) is that spikes in blood sugar levels cause or at least aggravate fat. I base this on the fact that I lost a bunch of weight on the diet, and even though I'm only halfway following said diet, the weight has stayed off.
While your conclusion that metabolism is one of the major factors in body weight is true, it ignores the fact that obesity rates have increases dramatically since the Second World War. I doubt that this is because people with slow metabolisms breed at a much higher rate, but rather that there has been a change in diet and lifestyle in general. It's the old nature vs nurture debate again.

I would say that both genetics and lifestyle are heavily intertwined in a way that it is very hard to discern which is the dominant factor in obesity. It's likely that we never be able to tell and leave them as just nature/nurture, just like space/time.

The two issues that I see as appearing since WWII are reduction in sleep time, and the explosion of the use of sugar, particularly in the form of high-fructose corn syrup. Children seem peculiarly vulnerable to HFCS, but the science is still pretty sparse.

Also, the cost of food in real dollars has come down a lot in the last forty years or so. People with the fat gene who might have stayed at least a little thinner may have picked up additional weight simply because eating more is cheap.

I agree that it's complex, and in fact that's the main thrust of this (long) post: That obesity is a complex business, and until we recognize the presence of that complexity, we will get nowhere in trying to address obesity as a public health issue.
Like all of the equations, exercise as a factor probably depends on the person. I tore a ligament in my knee, making me pretty much laid up on a couch in all my spare time after I'd been exercising regularly (medium impact, 1/2 hour to an hour per day) for six weeks. I put on about ten to twelve pounds. Because my knee's still not better, I'm doing the Weight Watchers plan with my husband. (Really, eliminating my peanut butter and chocolate intake would probably be enough, but it's easier to say no to myself about that factor when I'm actually on a food plan.) That's taking the weight gain back off--but I don't feel as healthy as I did when I was exercising regularly. I miss the work out.
The core problem with obesity is that people aren't paying attention to their own bodies; they're accepting what The Experts say.

The problem with accepting what The Experts say is that The Experts have good advice for the middle 60% of the Bell Curve. Another 20% can probably get away with it. That advice is probably wrong for the 10% at both ends of said curve.

Having one side of my family filled with people constantly fighting weight issues, and another branch fighting mood disorders, I have come to believe that anything you can ingest should be viewed as a pharmaceutical of some sort. It will make you feel better, worse, or nothing. It will affect your blood pressure, trigger hormone and endocrine responses, adrenaline responses, and all sorts of fun stuff.

I know people who overeat for the endorphin rush it causes. I know other people who over-exercise (IMO) for the same result. I know folks who have thyroid issues who have a horrible time controlling their weight, and who can't convince their doctors to increase the medication, because they're in the 'normal' range on tests.

I have a son, age 14, who eats a wheat-free diet due to allergy issues; he eats three meals a day, plus ice cream at night, yet is 5'6" tall (pushing 5'7") and weighs 85 pounds. If he were deliberately undereating, we'd call him anorexic. His doctor says he's fine. (I think the doctor likes having a data point that is at the other end of the Bell Curve, but that's a side issue.)

The bottom line is that every person has similar biology, but not *identical* biology. What works for me is not necessarily going to work for someone else. What's normal for me won't be normal for everyone.

My problem with people who are obese is that they aren't listening to their own bodies. They aren't paying attention to what happens when they eat different foods. They are trusting The Experts, when that clearly isn't working for them.

Yeah, it's not fair. I know that. You try telling a 7 yo that he can't have birthday cake because he's allergic to the wheat; it's no fun.

But it's necessary, for overall good health. Every person has to figure out their own, personal weird diet that keeps themselves healthy and relatively mentally stable, because as much as Western medicine wants us all to be standard-issue robots, we aren't.

(Anonymous)

Metabolic syndrome.

It's all about metabolism, the engineer
(evolution) did not design human body for office work and Big Macs.

http://en.wikipedia.org/wiki/Metabolic_syndrome

--Aki

Sleep and weight

Interesting data point is the correlation between more weight and sleep apnea. That can create a feedback loop between less sleep and more weight.

Also, I believe that our habit of eating out more and eating more prepared foods also contributes to weight gain.