Five Stealth Forces in Weight Loss
Scientists are zeroing in on the unexpected ways molecular forces—including genes and viruses—impact your weight. In the process, they're upending the conventional wisdom on just what makes a successful diet.
By Sora Song published July 1, 2008 - last reviewed on June 9, 2016
The various findings by public-health experts, physicians, psychologists, geneticists, molecular biologists, and nutritionists are about as similar as an elephant's tusk is to its tail. Some say obesity is largely predetermined by our genes and biology; others attribute it to an overabundance of fries, soda, and screen-sucking; still others think we're fat because of viral infection, insulin, or the metabolic conditions we encountered in the womb. "Everyone subscribes to their own little theory," says Robert Berkowitz, medical director of the Center for Weight and Eating Disorders at the University of Pennsylvania School of Medicine.
But within this fractured tableau, a few patterns now stand out clearly. A consensus is emerging that the conventional wisdom—eat less, exercise more—is inadequate at best. A quick look at our collective waistline makes it painfully clear the old equation—calories in minus calories out equals weight change—is fundamentally flawed. Research shows not every calorie is created equal, and different bodies use calories in different ways. We're programmed to hang onto the fat we have, and some people are predisposed to create and carry more fat than others. Diet and exercise help, but in the end the solution will inevitably be more complicated than pushing away the plate and going for a walk. "It's not as simple as 'You're fat because you're lazy,'" says Nikhil Dhurandhar, an associate professor at Pennington Biomedical Research Center in Baton Rouge. "Willpower is not a prerogative of thin people. It's distributed equally."
Science may still be years away from giving us a miracle formula for fat-loss. Until then, it's up to us, one paunchy individual at a time, to shed our extra flab. It's easier said than done, especially since we may have been doing it wrong all this time. But the newest, most unexpected findings from the front lines of diet research may yet help tip the scales in your favor.
Evolution: Your Body Wants You to be Fat
If you've ever tried to lose weight—be it 5 pounds or 50—you don't need to be told the human body resists weight change. We're each born with a predetermined set point—a weight range that typically spans about 10 to 20 pounds—and the further we push our weight away from it, the more intensely the body fights its way back. Hence the yo-yo effect: You diet and lose weight, only to gain it all back once you stop your diet. The culprit isn't lack of willpower, it's evolution.
The command center for the body's weight-management system resides in the hypothalamus—and it's calibrated to favor the preservation, rather than the elimination, of fat. That's accomplished through the hormone leptin, a crucial player in the brain's weight-management circuitry. Leptin is produced by the body's fat cells and signals the brain to regulate appetite and satiety—and, therefore, weight. If you lose body fat and leptin, it triggers hunger and the urge to eat; if you gain fat and increase leptin, you eat less. The more leptin your body produces, the leaner you tend to be; the less leptin you make, the higher your set point and the fatter you stay. Voila, the secret to set-point maintenance.
But things don't always go according to plan. The regulatory system can go awry: Some people produce too little leptin; others become desensitized to it. And when obese people lose weight, their leptin levels plummet along with their metabolism. The body becomes more efficient at using fuel and conserving fat, which makes it tough to keep the weight off. Obese dieters' bodies go into a state of chronic hunger, a feeling Rudolph Leibel, an obesity researcher at Columbia University, compares to thirst. "Some people might be able to tolerate chronic thirst, but the majority couldn't stand it," says Leibel. "Is that a behavioral problem—a lack of willpower? I don't think so."
Then what is it? In short, DNA. How the body maintains its regulatory mechanism may be largely under the influence of genes. According to some researchers, 70 percent of variation in people's weight may come from defects on genes, and many of those genes act on a common hunger-satiety pathway in the hypothalamus. One such gene is the melanocortin 4 receptor (MC4R), which communicates with leptin and triggers a feeling of fullness. When MC4R malfunctions, it causes overeating and obesity in animals and humans. Researchers estimate 6 percent of obese children and adults can trace their condition to a genetic defect that interferes with MC4R. But genes aren't destiny. When MC4R is disabled in mice, it causes overeating and obesity—unless they're allowed to exercise early on. In the end, weight is the result of a subtle dance between genes and environment.
Exercise: Why the Evening Walk Isn't Enough
The government has long espoused moderate daily exercise—of the evening-walk or take-the-stairs variety—but that may not do much to budge the needle on the scale. A 150-pound person burns only 150 calories on a half-hour walk, the equivalent of two apples. It's good for the heart, less so for the gut.
"Radical changes are necessary," says Deirdre Barrett, a psychologist at Harvard Medical School and author of Waistland. "People don't lose weight by choosing the small fries or taking a little walk every other day." Barrett suggests taking a cue from the members of the National Weight Control Registry (NWCR), a self-selected group of more than 5,000 successful weight-losers who have shed an average of 66 pounds and kept it off 5.5 years. Some registry members lost weight using low-carb diets; some went low-fat; others eliminated refined foods. Some did it on their own; others relied on counseling. But when it came to keeping weight off over the long term, they had one thing in common: vigorous exercise for at least an hour most days of the week. Most also participated in at least one other activity or sport. "People in the NWCR exercise a lot," says Barrett. She estimates they burn an extra 2,800 calories a week.
That said, not everyone can lose 66 pounds and not everyone needs to. The goal shouldn't be getting thin, but getting healthy. It's enough to whittle your weight down to the low end of your set range, says Jeffrey Friedman, a geneticist at Rockefeller University. Losing even 10 pounds vastly decreases your risk of diabetes, heart disease, and high blood pressure. The point is to not give up just because you don't look like a swimsuit model. "We focus on appearance because that's what everyone notices," says Friedman. "If there were no stigma, we wouldn't be worried about an unachievable goal. We'd just be worried about our health."
The Womb: Go Ahead, Blame Your Mother
The negotiation between your genes and the environment begins on day one. Your optimal weight, writ by genes, appears to get edited early on by conditions even before birth, inside the womb. If a woman has high blood-sugar levels while she's pregnant, her children are more likely to be overweight or obese, according to a study of almost 10,000 mother-child pairs.
Maternal diabetes may influence a child's obesity risk through a process called metabolic imprinting, says Teresa Hillier, an endocrinologist with Kaiser Permanente's Center for Health Research and the study's lead author. The mother's high blood sugar may mean the baby in the womb gets overfed, possibly pre-programming it for obesity. Even mothers whose blood sugar was at the upper end of the normal range had elevated risks of having overweight babies. The good news is that high blood sugar during pregnancy, known as gestational diabetes, is entirely avoidable: Children born to women who sought treatment for diabetes during pregnancy ended up no fatter than their peers.
The implication is clear: Weight may be established very early on, and obesity largely passed from mother to child. Numerous studies in both animals and humans have shown that a mother's obesity directly increases her child's risk for weight gain.
The best advice for moms-to-be: Get fit before you get pregnant. You'll reduce your risk of complications during pregnancy and increase your chances of having a normal-weight child. But if you think you're still at risk for gestational diabetes, make sure you get screened for hyperglycemia during pregnancy. If your blood sugar is high, talk to your doctor about treating it by modifying your diet and exercise. If that doesn't work, your doctor may prescribe insulin.
Insulin: The Great Diet Bake-Off
It's the $64,000 question: Which diets work? A yearlong government-funded study comparing Atkins, the Zone, Ornish, and LEARN (Lifestyle, Exercise, Attitudes, Relationships and Nutrition, based on the U.S. government's food pyramid) found all four work more or less, leading to short-term modest weight loss in overweight women. People on Atkins lost the most weight—an average of about 10 pounds—while participants on the other diets lost between 3.5 to 5.7 pounds on average.
Not exactly huge numbers. It got people wondering: Isn't there a better way to diet? Two months later another study seemed to offer an answer. The paper compared two groups of adults: those who, after eating, secreted high levels of insulin, a hormone that sweeps blood sugar out of the bloodstream and promotes its storage as fat, and those who secreted less. Within each group, half were put on a low-fat diet and half on a low-glycemic-load diet.
On average, the low-insulin-secreting group fared the same on both diets, losing nearly 10 pounds in the first six months—but they gained about half of it back by the end of the 18-month study. The high-insulin group didn't do as well on the low-fat plan, losing about 4.5 pounds, and gaining back more than half by the end.
But the most successful were the high-insulin-secretors on the low-glycemic-load diet. They lost nearly 13 pounds and kept it off. Their diet was designed to mitigate swings in blood sugar by replacing easily digested simple carbs—white bread, potatoes, fruit juice, cookies, and other refined foods—with vegetables, low-sugar fruits, and legumes.
Why were they so successful? The hormone insulin, which is secreted by the pancreas, is like a natural appetite suppressant. It's released when blood sugar rises, and it signals the brain that it's time to stop eating. When blood sugar and insulin drop too quickly, the brain takes it as a signal that it's time to feed, and so people feel hungry again sooner after eating—leading to overeating and weight gain.
How does your own insulin response measure up? Only a blood test can tell you for sure, but in general, low-secretors tend to be pear-shaped, carrying excess fat around the hips; high-secretors are apple-shaped, storing flab around the midsection.
The study's authors say it's too soon to give specific diet advice based on their findings, but health experts agree that regardless of your body shape, you'd do well to reduce or eliminate simple sugars and refined foods, like cookies, candy, and sugary sodas. Don't eliminate carbs altogether—even low-glycemic-load dieters got 40 percent of their calories from carbohydrates. Just replace easily digestible carbs with complex ones like fibrous veggies and fruits, brown rice, and whole grains.
Germs: Is Obesity Contagious?
What if your fat is caused not by diet or genes, but by germs—say, a virus? It sounds like a sci-fi horror movie, but research suggests some dimension of the obesity epidemic may be attributable to infection by common viruses, says Dhurandhar.
The idea of "infectobesity" came to him 20 years ago when he was a young doctor treating obesity in Bombay. He discovered that a local avian virus, SMAM-1, caused chickens to die, sickened with organ damage but also, strangely, with lots of abdominal fat.
In experiments, Dhurandhar found that SMAM-1-infected chickens became obese on the same diet as uninfected ones, which stayed svelte. He also found that nearly one in five overweight humans in his Bombay clinic showed antibodies—proving prior infection—and that they were about 33 pounds heavier than those never exposed.
He later moved to the U.S. and onto a bona fide human virus, adenovirus 36 (AD-36). In the lab, every species of animal Dhurandhar infected with the virus became obese—chickens got fat, mice got fat, even rhesus monkeys at the zoo that picked up the virus from the environment suddenly gained 15 percent of their body weight upon exposure.
The virus naturally infects 15 percent to 17 percent of the human population, says Dhurandhar, and is present in 30 percent of obese people—even nonobese people who have it have higher BMIs than their uninfected peers. "Even within that group, they were fatter," says Dhurandhar. "It could mean that's how they'll stay, or it could mean they were pre-obese."
For people who want to know whether they're infected, a Richmond, Virginia, company called Obetech offers an AD-36 antibody test. Although there's no way to rid your body of the virus, what the test can give you is a warning flag: If you find out you're infected, you can start eating healthfully and exercising now to try to stave off obesity later.
In his latest studies, Dhurandhar has isolated a gene that, when blocked from expressing itself, seems to turn off the virus's fattening power. Stem cells extracted from fat cells and then exposed to AD-36 reliably blossom into fat cells—but when stem cells are exposed to an AD-36 virus with the key gene inhibited, the stems cells don't differentiate. The gene appears to be necessary and sufficient to trigger AD-36-related obesity, and the goal is to use the research to create a sort of obesity vaccine.
Researchers have discovered 10 microbes so far that trigger obesity—seven of them viruses. It may be a long shot, but for people struggling desperately to be thin, even the possibility of an alternative cause of obesity offers some solace. "They feel better knowing there may be something beyond them that could be responsible," says Dhurandhar. "The thought that there could be something besides what they've heard all their lives—that they are greedy and lazy—helps."