Weight loss is a science, and a fascinating one at that. You won’t look at diets the same way after learning the facts behind today’s fat-busting finds.

Steven Blair is, in his own words, a “short, fat, bald guy.” But at five-foot-five and 200 pounds, he may very well be healthier than men much taller and leaner. He runs 25 miles a week, eats six to eight servings of fruits and vegetables a day, and avoids processed and fatty foods. A professor of exercise science and epidemiology at the University of South Carolina, Blair is a living example of how fat doesn’t play fair. And thanks to advances in his field, he is beginning to understand why.

Genes, hormonal imbalances, and even viruses are now acknowledged to play a role in obesity. Eating less and working out more, in fact, don’t have nearly as much to do with weight loss as you might assume. “This is all counter to what people think they know,” says Blair. “You can see obesity, so it’s easy to say ‘Well, that person must not be trying. He must be lazy.’ But that’s often not the case.”

Our team pored over the latest studies, interviewed the top clinicians in obesity science, and listened to the real-life experiences of men and women struggling to maintain their weight. Here, the latest (and often unexpected) thinking behind size and thighs, fatness and fitness.

1. It Really Is Genetic

When scientists first discovered it in certain chubby mice, they called it simply the fatso gene. Years later, when they scoured the human genome for markers that increased vulnerability to type 2 diabetes, the fatso gene (now more politely called FTO) showed up there too. Turns out, people with two copies of the gene were 40 percent more likely to have diabetes and 60 percent more likely to be obese than those without it. Those with only one copy of the gene weighed more too.

Scientists now suspect that there are lots of fat genes. “There could be as many as 100 of them,” says Claude Bouchard, PhD, executive director of the Pennington Biomedical Research Center at Louisiana State University System, “each adding a couple of pounds here and a pound or two there. That’s a noticeable difference when it comes to how much more fat we need to burn off.”

As much as 16 percent of the population has two copies of the FTO gene, and half of us have one copy. So far, scientists suspect that the other possible obesity-promoting genes have a small effect compared with FTO. The good news? “A genetic predisposition isn’t necessarily a life sentence,” says Bouchard. Exercising regularly can offset the risk.

2. Some People Just Have More Fat Cells

And the range is enormous, with some people having twice as many fat cells as others have, says Kirsty Spalding, PhD, of the Karolinska Institute in Stockholm. Even if you’ve lost a few pounds (or gained some), your fat-cell count remains, holding tight to the fat already inside and forever thirsting to be filled up with more. (To add insult to injury, the fat cells of overweight and obese people hold more fat too.)

New fat cells emerge during childhood but seem to stop by adolescence. Those of us destined to have a lot of these cells probably start producing them as young as age two. The cells’ rate of growth may be faster, too—even if kids cut way back on calories.

Strangers have written to Spalding, telling her how depressed they are by her research. But she says her news isn’t all bleak. You’re better off with more fat cells, she says, than with fewer fat cells that become overstuffed and enlarged. (New research suggests that the overstuffed group are more vulnerable to obesity-related health complications.) So while you can’t reduce your total number of fat cells, there are things you can do to keep them small. (See next point.)

3. You Can Change Your Metabolism

Another Scandinavian team looked into what happens at the cellular level when you gain weight. Kirsi Pietiläinen, PhD, an assistant professor of nutrition at Helsinki University Central Hospital, studied sets of twins where one was fat and the other thin, and learned that fat cells in heavier twins underwent metabolic changes that make it more difficult to burn fat. Pietiläinen’s team suspects that gaining as little as 11 pounds can slow metabolism and send you spiraling into a vicious cycle: As you gain more fat, it becomes harder to lose it.

How to get back on track? “The more I learn on the job, the more I’m convinced we need physical activity,” Pietiläinen says. Once a chubby child herself, she now runs regularly and is at a healthy weight.

4. Stress Fattens You Up

The most direct route is the food-in-mouth syndrome: Stressful circumstances (your bank account, your boss) spark cravings for carbohydrate-rich snack foods, which in turn calm stress hormones. (When researchers in one study took away high-carb food from stressed mice, their stress hormones surged.)

Stress hormones also ramp up fat storage. For our prehistoric ancestors, stress meant drought or approaching tigers, and a rapid-storage process made sense; we needed the extra energy to survive food shortages or do battle. Today we take our stress sitting down—and the unused calories accumulate in our midsection.

To whittle yourself back down to size, in addition to your usual workout routine, make time for stress relief—whether it’s a yoga class or quality time with family.

5. Mom’s Pregnancy Sealed Your Fate

A mother’s cigarettes increase the risk of low birth weight, and alcohol can damage her baby’s brain. So why wouldn’t unhealthy foods wreak similar havoc? A growing body of science suggests that sugary and fatty foods, consumed even before you’re born, do exactly that. A Pennington study on rodents reports that overweight females have higher levels of glucose and free fatty acids floating around in the womb than normal-weight ones do. These molecules trigger the release of proteins that can upset the appetite-control and metabolic systems in the developing brain.

What’s true for mice is often true for humans too. Doctors from State University of New York Downstate Medical Center compared children born before their mothers had gastric bypass surgery with siblings born later. Women weighed less after the surgery, as expected, but their children were also half as likely to be obese. Because siblings have such similar genetic profiles, the researchers attributed the weight differences to changes in the womb environment. Moms-to-be, take note: You can give your kids a head start by eating well before they’re born.

6. Sleep More, Lose More

When patients see Louis Aronne, MD, past president of the Obesity Society and author of the forthcoming book The Skinny, they’re as likely to have their sleep assessed as their eating habits. If patients are getting less than seven to eight hours, Dr. Aronne may prescribe more shut-eye rather than the latest diet or drug. With more sleep, he says, “they have a greater sense of fullness, and they’ll spontaneously lose weight.”

Why? University of Chicago researchers reported that sleep deprivation upsets our hormone balance, triggering both a decrease in leptin (which helps you feel full) and an increase of ghrelin (which triggers hunger). As a result, we think we’re hungry even though we aren’t—and so we eat. Indeed, sleep may be the cheapest and easiest obesity treatment there is.

7. Your Spouse’s Weight Matters

When Jodi Dixon’s six-foot-two, 360-pound husband lost 125 pounds, she had mixed feelings. She was the one who always watched her weight and exercised; she was always the one trying to get her husband to be more active. Mort, a medical sales rep, was always the life of the party, says his wife, a 43-year-old mother of two in Freehold, New Jersey. But when he lost the weight, it was different.

“Men and women would flock to him, drawn to his charisma,” she recalls. “I felt jealous.” Dixon comforted herself with food and gained 20 pounds before she decided to take action. She began biking with her husband and enrolled in a diet program. Eventually she trimmed down, too, shedding 30 pounds, and has her sights on losing more.

Dixon credits the weight gain, and the loss, to her jealousy. But research shows that weight gain and loss can be, well, contagious. A study in the New England Journal of Medicine suggests that if one spouse is obese, the other is 37 percent more likely to become obese too. The researchers concluded that obesity seems to spread through social networks.

As in Dixon’s case, slimming down seems to be catching, at least within the family: When Dixon launched her weight-loss plan, her eldest daughter, also overweight, followed her mom’s healthy habits and lost 40 pounds.

8. Achoo! A Virus Can Cause Obesity

Adenoviruses are responsible for a host of ills, from upper respiratory tract problems to gastrointestinal troubles. The link to fat was uncovered when researchers at the University of Wisconsin injected chickens with the viruses and found that certain strains fattened them up.

Stem cells, known for their chameleonlike abilities to transform, also turned into fat cells when infected with the viruses. “The virus seems to increase the number of fat cells in the body as well as the fat content of these cells,” says Nikhil Dhurandhar, PhD, now an associate professor of infections and obesity at Pennington.

Human studies, including comparisons of twins, suggest that obese people are indeed more likely to harbor antibodies for a particular virus, known as adenovirus-36.

We have flu shots; could an obesity vaccine be the next step? It may sound far-fetched, but “that’s what they said about cervical cancer too,” says Dhurandhar.

9. Cookies Really Are Addictive

While food is not addictive the way cocaine or alcohol is, scientists in recent years have found some uncanny similarities. When subjects at Monell Chemical Senses Center in Philadelphia were shown the names of foods they liked, the parts of the brain that got excited were the same parts activated in drug addicts. It may have to do with dopamine, the hormone linked to motivation and pleasure, say researchers at Brookhaven National Laboratory in Upton, New York. If obese people have fewer dopamine receptors, they may need more food to get that pleasurable reaction.

10. Ear Infections Can Taint Your Taste Buds

For years, the team at Linda Bartoshuk’s taste lab at the University of Florida wondered why people who tasted food less intensely than others seemed more likely to be fat. Researcher Derek Snyder had a theory: Could an ear infection, which can damage a taste nerve running through the middle ear, be the missing link? After tabulating 6,584 questionnaires, the team discovered that those over 35 who had suffered several ear infections had almost double the chance of being obese.

Responses to additional questions provided clues as to why. Former ear-infection patients were a little more likely to love sweets and fatty foods—perhaps because the damaged nerve causes them to have a higher threshold for sensing sweetness and fattiness. Even a small increase in calories from bad food choices adds up over time.

Childhood ear infections are as hard to avoid as the colds that tend to bring them on, but limiting passive smoke seems to drive down incidents of ear infection. If you’re an overweight adult who suffered a severe ear infection as a child, it may be worth paying attention to the taste and texture of your food. Simply finding healthier substitutes, such as fruit instead of candy, or olive oil instead of butter, may help drive you toward eating better and weighing less.

11. Antioxidants Are Also Anti-Fat

Free radicals are now blamed not only for making you look old but also for making you fat. Zane Andrews, PhD, a neuroendocrinologist at Monash University in Australia, says these oxidizing molecules damage the cells that tell us we’re full. Free radicals emerge when we eat (something even the keenest dieter must do to survive), but they’re especially prevalent when we gorge on candy bars, chips, and other carbohydrates. With every passing year, these fullness signifiers suffer wear and tear-causing the “stop eating!” signal to get weaker and appetites (and possibly our stomachs) to get bigger. The best way to fight back? Avoid the junk and load up on colorful, antioxidant-rich fruits and vegetables.

12. Pick a Diet, Any Diet

As established diet books constantly reinvent themselves to sell copies and win converts, a curious phenomenon has emerged: Ornish, Atkins, and everyone in between are sounding remarkably similar. The low-fat gurus now say that certain fats are okay, while the low-carb proponents are beginning to endorse whole grains. With every new guideline and selling point, each diet acknowledges that there are really four basic rules to healthy eating (drumroll, please):

Consume carbs in the form of whole grains and fiber.

Avoid trans fats and saturated fats.

Eat lean protein.

Fill up on fruits and vegetables.

The low-carb South Beach Diet, for example, now espouses the virtues of eating the Mediterranean way-including lots of carbohydrate-rich fruits and vegetables. The latest Atkins book emphasizes the “good carb” message too. Weight Watchers, a champion of the points system, is now offering a “no counting” option based on healthy choices like those above. Jenny Craig is pushing Volumetrics, a high-volume, low-calorie strategy. And everyone gives a thumbs-down to processed and sugary carbohydrates, which cause insulin to spike and can lead to more fat and even diabetes.

Low-fat-diet guru Dean Ornish, MD, says, “It’s the end of the diet wars.” His most recent book, The Spectrum, even offers recipes that can be prepared in various “degrees”—from a vegetable chili served plain (low-fat) to one served with olives (more fat) to still another served with turkey breast sausage (still more fat).

The key to all of this, of course, is moderation rather than deprivation—eating in a way you can live with. And for some people, an important side effect of eating more plant-based foods is that it’s better for the environment. (See food writer Mark Bittman’s Simple Till Six: An Eating Plan for Busy People.)

13. You Can Be Fat and Fit

A growing body of literature suggests that size doesn’t matter when it comes to your health. A study published in the Archives of Internal Medicine surveyed 5,440 American adults and found that 51 percent of the overweight and almost 32 percent of the obese had mostly normal cholesterol, blood sugar, blood pressure, and other measures of good health.

Further defying conventional wisdom, the article also reported that 23.5 percent of trim adults were, in fact, metabolically abnormal—making them more vulnerable to heart disease than their heavier counterparts.

The latest U.S. Department of Health and Human Services report corroborates what our doctors have said all along: You need about 30 minutes of moderate-intensity physical activity five days a week for health. And you don’t even have to do your exercise in one fell swoop—ten-minute stints of walking are just as effective. That means if you forgo the elevators for the stairs, get off one train or bus stop earlier, and park your car a few blocks away, chances are you’ll be good for the day.

Remember Steven Blair, the self-described short, fat, bald guy? At age 69, his blood pressure is in check, his cholesterol levels are normal, and his heart is strong. What’s more, he may have even more positive vital signs, according to his recent study in the journal Obesity: Men who are fit (determined by their performance on a treadmill) have a lower risk of dying of cancer than out-of-shape guys, regardless of their body mass index, waist size, or percentage of body fat.

The news is heartening, says Blair: “We don’t have great tools to change people’s weight, but we know we can change their fitness levels.

New Way to Tame Cravings?

Some of the most eagerly awaited pills in the pipeline promise to calm cravings, reduce appetite, and even boost metabolism.

For instance, vigabatrin has been studied as a treatment for drug addiction. Suspecting that it would work on weight-control patients, scientists injected the substance into obese rats. It worked: The rats lost 19 percent of their original weight after 40 days.

Another drug, tesofensine, works on three different mechanisms in the brain to regulate appetite and metabolism. In early trials, patients who used the drug lost an average of nearly 30 pounds.

So what’s the catch? Side effects. The much-hyped drugs taranabant and Acomplia both failed because they caused severe mood swings and depression. Scientists will have to pay close attention to dosage and side effects if future weight-loss drugs are to clear the FDA approval process.