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Who's in charge—you or your appetite? Eating right would be a piece of cake if it weren't for that overpowering urge called hunger. But where do those "feeeeed me!" signals really come from? Your genes? Our culture? The mysterious hunger hormones leptin and ghrelin?
Like the insatiable houseplant in Little Shop of Horrors our bodies send a message to our brains: "Feeeeed me!" The monster within us makes its relentless demand, we comply, and soon enough it rears its ugly head yet again and roars for more.

We're supposed to feel hungry when we need fuel, but hunger has become so fraught, so linked to our collectively ballooning girth, that it often seems less like a finely tuned bodily function and more like a beast in need of taming. Who's in charge—our appetites or our brains? And is there really such a thing as willpower?

The answer to the second question is yes, of course, but if we try to live by willpower alone—to eat less than nature intended us to eat, to be thinner than our genes meant for us to be—we're in for a struggle. The sad truth is that for some people, staying thin means going hungry. The much happier truth is that scientists are beginning to understand much more about how we know when, and how much, to eat. Millions of people, from the clinically obese to those struggling with an extra five pounds, stand to gain (and lose) from the researchers' insights.

A major advance in Big Pang theory came in 1995, with the discovery of leptin, the first recognized hormone that regulates body weight. "Since then, the pace of change in understanding appetite control has been exponential," says David E. Cummings, MD, associate professor of medicine at the University of Washington in Seattle. Two years ago, Cummings himself reported that surges of another hormone, ghrelin, prompt hunger before meals. Both breakthroughs have brought us much closer to figuring out how, when, and why the creature must be fed.

In a perfect world, two to three and a half hours after eating breakfast, your empty stomach secretes ghrelin, which travels to the brain and triggers your appetite. You begin to feel physically hungry, you think about lunch, and pretty soon you're eating. The food then signals your ghrelin levels to drop off, decreasing your appetite.

As you eat, other molecules and hormones—including PYY, which was recently found to have a role in hunger—tell your brain to stop eating: Your stomach expands, and nerve impulses from the stretch receptors there, as well as hormones stimulated by food in the intestine, alert the brain that you're full. Together, ghrelin and PYY are part of a tag team of hunger, turning appetite on, then off.

Leptin also turns your appetite off, but in a longer-term way than PYY: It lets your brain know how much fat you've stored in your body. Leptin is made by the fat cells, and as fat stores rise, more leptin is secreted, traveling to the brain with the message You're fat enough—stop eating so much. If fat levels fall, so do leptin levels, and appetite increases. Mice that are genetically unable to produce leptin grow enormously obese because they never get the word to stop eating.
This elaborate chemical dance is a brilliant system, capable of balancing food intake with what Jeffrey Friedman, MD, PhD, who led the team that discovered leptin, calls "an extraordinary level of precision." Unless, that is, there's a glitch in your particular system. One glitch, says Friedman, a medical researcher at the Howard Hughes Medical Institute at Rockefeller University, is that "for some reason, obese people appear to be resistant to leptin, which is probably part of the reason they're fat": The leptin message—to eat less—isn't getting through. Another problem isn't really a glitch as much as a very clever (too clever) refinement of the system. Lots of evidence now suggests that your genes determine your personal ballpark body weight, or set point, and that hunger is one of your body's tools to keep you right there. When you try to diverge from your set point by becoming thinner or fatter than nature decrees, your entire chemical system kicks into gear to pull you back.

When you diet, your metabolism slows down to conserve calories. At the same time, your hunger increases dramatically, regardless of your need to lose weight. "The 300-pounder who goes to 285 will feel very hungry," Cummings says. "The 100-pounder who goes to 95 will also feel very hungry."

One reason, he explains, is that when you lose weight, ghrelin levels not only spike before mealtimes but also rise overall. "You'll still have three spikes a day, plus the whole level shifts upward," Cummings says. "The troughs and peaks are all higher than before losing weight. And these changes appear durable—they don't seem to go away even if you stay below your natural point for more than six months. Over time, they erode willpower." As fat stores go down, so does leptin, and your brain gets an unrestrained hormonal signal to eat more. "The evidence suggests," Friedman says, "that people who have lost weight below their personal set point are hungry a lot of the time."

You can probably guess why all these systems kick into gear when you lose weight: To your genetic code, this restraint looks like starvation. "People have an illusion that they can consciously control their food intake," Friedman says. "That's true over the short term, but over the longer term the biological drive to eat enough to get your weight back to your individual level almost always overcomes your conscious control."

Outside Influences
Wait a minute—we're more than just animals, right? We've got highly evolved brains full of thoughts and emotions and plans for a bikini summer, and surely we can tell our bodies what to do. It also seems clear to our logical brains that there are other things besides hormones that prompt us to eat. The biggest factor, even die-hard biologists like Cummings and Friedman say, is the environment—everything from food smells and portion sizes to emotional connections to food dating back to childhood.

It's well documented, for instance, that an environment of many flavors prods us to eat more and keeps us hungry. Megan McCrory, PhD, a nutritional scientist at Tufts University, puts hunger and appetite into separate categories. "Hunger is a physiological feeling, while appetite is the desire to eat a certain food or foods," she explains, and that desire—that craving—gets turned on by our having lots of choices. "We want to try all of the great variety of flavors available," McCrory says. "And when we eat a little bit of everything, we tend not to keep the calories the same as when we're eating only one or two foods." She says that studies have shown that we eat 25 percent more, on average, in a single meal when more variety is available.

This so-called buffet binge may help explain why some restrictive diets, like Atkins, work—at first. How many meals of steak and eggs can you eat before you lose interest in eating them, and are driven to eat carbs?

An environment that constantly offers lots of carbs can also spur hunger. High-glycemic-index (GI) foods like potatoes and white bread break down quickly into glucose, which causes a spike in blood sugar levels, followed by insulin release, which pushes blood sugar down. Your body wants to bring blood sugar back up to normal—and what quicker way than with another cinnamon bun or bagel? "Of all the studies that have shown the effects of GI on appetite," says David Ludwig, MD, PhD, associate professor of pediatrics at Harvard Medical School and director of the obesity program at Children's Hospital Boston, "virtually all showed that high-glycemic-index meals make you hungrier sooner after eating. In our own study of obese teenagers, after a high-GI meal they wound up eating many more calories than if the previous meal was low-glycemic-index."

Mind Over Stomach?
While our culture offers infinitely more temptations than the prehistoric world of our ancestors (they didn't watch commercials for hamburgers at 9 P.M.), what about the environment in our minds? Any number of forces conspire to lure us to the fridge: stress, boredom, celebration, misery, and that old standby "It's time to eat." Whether it's our psychological state or our hardwired nature that predominates is the question that most divides biologists and behaviorists, with the former saying that most of our eating habits are preordained and the latter believing that much about hunger can be taught, controlled, or unlearned.

Susan Head, PhD, a clinical and health psychologist in private practice in Durham, North Carolina, helps patients with the emotional side of obesity and dieting, as she previously did at the Duke Diet & Fitness Center. Head identifies two misuses of hunger, both of which lead to overeating. One has to do with that enticing exterior environment, where portions have expanded and food is everywhere. "A lot of people are eating unconsciously these days," Head says. "They don't wait till they're hungry. They're eating like robots. The doughnuts are there—say, at a meeting—and people eat them." For them, eating is about availability, appetite (desiring food), and scheduling ("Lunchtime!"). Hunger has nothing to do with it.

The other kind of overeater has absorbed the ambient cultural anxiety about weight and enjoys the feeling of being hungry (or at least of being "not full") because, Head says, "being not full means I'm losing weight—hunger is good." So she puts off eating through the early stages of hunger—which include having thoughts about food and a vague empty feeling—until she reaches the growling- or aching-stomach stage, at which point she could eat a horse, and often does (or the equivalent in pizza).

Taken to the extreme, such hunger denial is expressed as anorexia, which is an example of the power of the mind, or will, over the demands of the body. Anorexics, Head says, don't even admit they're hungry; they define that starving feeling as "success." Their eating experience is so dominated by rules, and has so little to do with what their bodies are telling them, that they have redefined all the terms to express it. "Anorexics are way too insensitive to hunger and way too sensitive to fullness," Head explains. "Any absence of hunger is 'full'"—and while full feels comforting and soothing to most people, it feels terrifying to the anorexic.

Head believes that all of these habits—unconscious eating, hunger denial followed by overeating, and eating disorders like anorexia—can be broken. Both overeaters and undereaters are trying to ignore what's actually an essential internal meter for good eating. Head works with tried-and-true tools to get the hunger apparatus working again. Patients use hunger scales to rate their hunger and fullness from 1 to 10, relearning what hunger feels like and when to respond to it. They also learn to redefine fullness or satisfaction so that it doesn't mean "stuffed."

Pill Power
Some people can go a good part of the day without food; others become ravenous without regular feeding. Some are full after half a cheeseburger; others finish one and want a few more. Are such differences all in our heads?

Our minds and bodies are so linked that sometimes what seems psychological is almost completely biological or chemical in nature. This became clear long ago in regard to hunger, when an American researcher during World War II put a group of volunteers on a semistarvation diet to study how to help victims of wartime famine. As the men lost an average of 25 percent of their body weight, they became not only sluggish and cold (signs of a slowed metabolism) but also obsessed: They were constantly hungry, they talked and thought and daydreamed about food, they read cookbooks and fantasized about meals, they carefully guarded their rations from others, they became increasingly irritable with one another.

Eating-disorder experts have come to recognize, in light of this study and others, that some psychological symptoms of anorexia nervosa—obsessing about food, hoarding it—occur as a biological response to deprivation. Rather than stemming from some neurotic fixation, these symptoms appear because the body is screaming "Eat!"—as it does whenever a person's weight has dropped below the set point.
This could all sound depressing to anyone who has been battling her own hunger cues for years, but researchers like Cummings have a different view. "If you're born with obese genes," he says, "now you know it's not your fault. A lot of overweight people realize that their bodies have fought their efforts to lose weight, but those around them have always faulted their willpower."

For people to really curb hunger, Friedman anticipates drug therapies that manipulate (and outsmart) chemical signals—therapies that are already in the animal-testing stage. "We're looking at it the way you'd look at any other medical problem, like cancer," Friedman says. "You figure out how the system normally works, then figure out what's different when you have the disorder, then develop therapies." For hunger and overeating, Cummings says, one very promising research direction is a ghrelin blocker, now in preclinical studies, that would stop ghrelin from acting on the parts of the brain that trigger hunger. Researchers are also pursuing the use of PYY as a possible long-term treatment for obesity.

Once we have "the equivalent of Prozac for obesity," Friedman says, people may finally begin to believe that big appetites and big bodies are the result of more than "simply a set of bad lifestyle choices." But if, in the view of biologists like Cummings and Friedman, hunger is primarily an unbending fact of nature, how do they explain the enormous rise in obesity over the past two decades? It's not that our genes have altered in 20 years to make so many more of us fat, Friedman says. Rather, across the population there has been an average weight gain of seven to ten pounds in the past decade that's still within the approximately ten-pound range of variation that many people's set points allow them. This overall weight gain, attributable mainly to environment, he says, has pushed a certain percentage of the population over the border into the range of obese. Those whose genes gave them a blueprint for slenderness, meanwhile, have remained at much the same weight.

So how might a Prozac for hunger change this situation? Those who have a major wiring problem will benefit from drug treatment, and the rest will have to cope on their own—the same way people with the ordinary blues rather than clinical depression come to terms with their problems and learn behavioral strategies to feel better. Mentally, that could mean shooting for a reasonable, livable weight toward the low end of your set point. Practically, it means avoiding buffets or big loads of refined carbs, becoming sensitive to your personal hunger-rating scale, and simply stopping to think before overeating. "If you're craving a half-gallon of ice cream every night," Head says, "I wouldn't trust that craving." She suggests asking yourself, What else is going on in my life? Am I feeling lonely and depressed? If so, a half-gallon of ice cream isn't going to solve that—although a dish of ice cream, eaten slowly enough so that all those little satiation nerve signals get activated, might make a tasty compromise.

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