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April 25th, 2024

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So, your genes can build a diet that gets you in your jeans?

Tamar Haspel

By Tamar Haspel The Washington Post

Published Oct. 28, 2019

So many diets, so little impact on skyrocketing obesity rates! But, somehow, the failure of yesterday's diet du jour never seems to dampen enthusiasm for tomorrow's. Case in point: personalized diets, tailored for your DNA.

Obesity absolutely, positively has a genetic component, but to figure out whether knowing your genome can help you zero in on a diet that's appropriate for you, you have to understand what those genes do.

If you get on the scale in the morning and don't like what you see, and then read a headline about, say, a "weight gain gene," your first thought may be a very straightforward effect: Your metabolism is slower than other people's.

Yes, some people do run more efficiently than others. If you and I are the same age, weight and gender, and our body fat percentage is the same, our base metabolism - the stuff that keeps our organs working and our temperature constant - "might vary on average 200 calories," says Eric Ravussin, director of the Nutrition Obesity Research Center at Louisiana State University. "The extreme can be plus or minus 200 calories; you can be 400 calories apart."

Four hundred calories isn't chump change. It means you can have a grande Mocha Frappuccino every single day and I can't. Or vice versa. So I asked whether that difference can account for the obesity epidemic.

Ravussin, who seems like a perfectly nice person, didn't say, "What a stupid question," but he sounded a little incredulous. "I don't think it explains our obesity epidemic. The genes, the biology hasn't changed over the past 50 years. Weight gain is the result of interactions of your biology and the environment. What has changed drastically is the environment."

Although some part of those 400 calories you and I might vary by is genetic, that's not what's mostly at play here. Ruth Loos, a professor at the Icahn School of Medicine at Mount Sinai in New York, wrote in an email that the contribution of resting metabolic rate to obesity "is small and the genetic component is very likely to be small as well."

Okay then, what is it? "The brain-regulating hedonic aspects of food intake are very likely to be much bigger," wrote Loos.

That "hedonic" part needs a little explanation. There are basically two reasons we eat. The first is to live; we respond to internal hunger and satiety cues to regulate our intake. That's called homeostatic eating. But anyone who's ever found room for dessert after a big meal knows that there's being full, and then there's blueberry pie.

We don't just eat for sustenance. We also eat for pleasure - hedonic eating - and although the two kinds aren't completely separate, they are governed in different ways. Hedonic eating involves the reward circuitry in your brain, and deliciousness takes satiety to the cleaners. The 40% to 70% of obesity that is thought to be heritable (Loos finds 50 percent to be a reasonable estimate) is operating primarily in deliciousness territory, not in metabolism territory. "We find the genes are implicated in eating behavior," says Loos.

No expert I've ever spoken with about this believes we have anything close to all the answers. Giles Yeo, a researcher at the University of Cambridge and the author of "Gene Eating: The Science of Obesity and the Truth About Diets," says more than 300 genes appear to play a role in obesity - so far - and researchers are just beginning to figure out what they do.

From what we do know, says Yeo, "it's the brain." Partly, that's how we experience hunger. It's also how we experience the reward element of food. "Genetic propensity to obesity is a propensity to eat more."

In the face of our modern food environment (read: tempting, convenient, cheap, calorie-dense food coming at you 24/7), some of us are genetically predisposed to weight gain. We hear the call of food louder. And some of us are also better at resisting it. Both Loos and Yeo told me that willpower probably also has a genetic component (something we can say of "the vast majority of human traits, plausibly all," says Yeo), and that, too, comes into play.

But let's step away from the genome. The conversation about the 50%, give or take, of obesity that's genetic isn't complete without the 50% that isn't. It's "lifestyle, different diets, different neighborhoods, different medications," says Loos.

All of those things are related to socioeconomic status, and it turns out that matters a lot. Clare Llewellyn, an associate professor at University College London, studies the genetic component of obesity by studying twins, and she has found that the higher you go up the socioeconomic scale, the less your genes matter.

What's happening in homes, with individuals, is a microcosm of what's happening societally. "If you're reared in an environment where you have access to highly palatable food, the child will respond to those food cues by eating. If you're the same [genetically], but reared in an environment with lots of fruits and vegetables on show, model behavior by parents, you're not going to have the opportunity for those genes to be expressed."

Good to know that growing up in a nice neighborhood with an affluent and well-educated family mitigates a genetic propensity to obesity, but is that really useful information to those of us who fight our weight?

In a way, it is. In fact, I think it's key. It tells us the environment is the difference between whether somebody dealt a lousy genetic hand gains weight or doesn't. Before about 1950, few of us faced an obesogenic environment. Now, we all do, and the further down the socioeconomic scale you happen to be, the worse it is.

So the food environment has to change. Which pretty much everyone agrees on. But while we continue to argue about a sugar tax and zoning restrictions on fast-food outlets and school lunch standards, is there anything we, the people, can do in the meantime?

I'm sorry to report that neither Llewellyn nor Yeo is terribly optimistic about how successfully individuals can navigate this environment without changes coming from government and corporate sectors, but the direction of the effort we all need to make is clear: Control whatever parts of the environment you can.

Over some 20 years talking to scientists about genes and obesity, there's one thing I never heard: Try the [fill in the blank] diet. These researchers are definitely not singing out of the diet industry's hymn book. Nobody mentions leptin or insulin or carbohydrate metabolism. Diets are about biology; geneticists talk behavior.

Which leaves me very, very skeptical about the future of personalized diets for weight loss. If the genetic component is more about how you respond to food - how delicious it is to you, how sensitive you are to hunger signals, how effectively you manage temptation - the genes that control, say, your insulin response may not be terribly relevant. Since all these things are interconnected, never say never, but my crystal ball says personalized diets won't be any better than garden-variety, unpersonalized diets.

Of course, the personal attention and belief that "this time, it's personal" may help strengthen people's resolve, in which case the diet may indeed be more effective. I eagerly await the controlled trial where half the participants are told the assigned diet is genome-based while the other half are told it's just another diet.

As much as I would like to report that understanding obesity's genetic roots can help us all lose weight, I'm afraid I can't. But what it does tell us is that, by focusing so inexorably on biology, we're missing the boat. "Genes load the gun, and the environment pulls the trigger," Loos told me.

Low-fat and low-carb and South Beach and paleo and Whole30 and keto and vegan are the deck chairs we've been rearranging for decades now. Iceberg, dead ahead.

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