Such findings should come as no surprise; eating is more important to an individual's survival than even sex, and it's in everybody's interest to make sure the urge to consume stays strong. If you're one of the millions trying to lose weight or lower your cholesterol, you know firsthand just how powerful a force appetite can be. In this land of plenty, where there's little chance of starving, our appetites have become downright dangerous.
"We're overeating, eating way beyond our caloric need," says Mary Boggiano, a psychologist at UAB. "Sixty-four percent of the population is overweight." Half that number—fully one-third of the U.S. population—is not just overweight but obese, facing increased risks of heart disease, high blood pressure, cancer, diabetes, and arthritis. The steep rise in obesity over the past two decades has been called an epidemic and deemed a factor in hundreds of thousands of deaths a year. Despite policies aimed at reversing the trend, "current data indicate that the situation is worsening," warns the U.S. Centers for Disease Control and Prevention.
So researchers are studying rat junkies—and human subjects, too—in the hopes that a deeper understanding of appetite will yield strategies to obstruct it. The studies explore psychology as well as physiology because, as every dieter knows, appetite afflicts the mind as much as the body. Hunger and craving may originate in the flesh, but they manifest in that zone of consciousness where want and need are easily confused. To clarify the difference, it helps to distinguish between "brain hunger"—the mind's desire to eat for pleasure—and "stomach hunger"—the body's demand to eat for energy.
"It doesn't take that much food to quell stomach-hunger pains," says Boggiano, who struggled with bulimia for years. Rather, it's brain hunger, she says, that triggers bingeing behavior and cravings for specific foods. A double whammy of brain and stomach hunger may make it feel impossible to trim off extra pounds. It's clear no theory of appetite will succeed unless it can account for both kinds of hunger. No diet will, either.
The Orchestra Within
Stomach hunger is appetite at its most basic. It's created by a network of interrelated metabolic pathways that monitor and maintain the body's energy status in a balance known as homeostasis. If you skip dinner to work late and get stuck in traffic on the way home, your growling stomach will remind you that regular meals are a necessity, not a luxury. An empty stomach churns out a hormone called ghrelin, which stimulates hunger; and as blood-sugar levels drop between meals, the level of insulin in the bloodstream declines, too. If you pull over and get a bite to eat, your blood sugar and insulin levels will spike, and a hormone called leptin, produced by fatty tissue, will be released to initiate feelings of satiety. These visceral messengers—ghrelin, leptin, blood sugar, insulin—and others communicate with the central nervous system, whose job it is to stir up or discourage appetite.
The relay center that translates into hunger or satiety all the metabolic signals from the outlying districts is the hypothalamus, a cherry-size structure deep in the brain. Its central role in appetite regulation was clearly demonstrated in the 1940s, when scientists discovered that rats with surgical damage to a region of the hypothalamus called the ventromedial nucleus ate voraciously. The postoperative animals, barely recovered from anesthesia, chowed down with such abandon that some literally inhaled food particles until they had trouble breathing. They gained more than 10 percent of their body weight in the first 18 hours post-op.
People with comparable brain lesions behave the same way. In the 1960s, doctors admitted to New York Hospital a young woman with a hypothalamic tumor who threw fits of violent rage whenever food was withheld from her. In two months at the hospital, the woman gained nearly a pound a day before dying of a heart attack. Such observations amply confirmed that the ventromedial hypothalamus (VMH) is the satiety center, in charge of suppressing appetite. In the 1950s, a nearby region—the lateral hypothalamus (LH)—was implicated in triggering appetite. Rats with LH lesions ate less and got skinny.
That simple anatomical model has since been supplanted by a more elaborate biochemical one, in which a web of neurotransmitters, hormones, peptides, and receptors works within and beyond the hypothalamus to help maintain the body's energy balance. Neuroscientist Satya Kalra of the University of Florida at Gainesville calls it the "appetite-regulating orchestra," and it does have a symphonic complexity. The stomach's hunger hormone ghrelin, for example, acts on the hypothalamus to stimulate the release of neuropeptide Y, the most potent appetite enhancer yet discovered. Ghrelin also suppresses the production of proopiomelanocortin (POMC), an appetite inhibitor, in the hypothalamus.
Conversely, the fat-cell satiety factor leptin slows production of neuropeptide Y and promotes POMC production. Cells in the hypothalamus also have receptors for insulin and blood sugar that utilize these same pathways to slow production of NPY and activate POMC release. Some visceral signals reach the brain via nerve cells rather than the bloodstream. A satiety peptide called cholecystokinin (CCK), for instance, released in the small intestine, may work by directly triggering the vagus nerve, which runs from the gut to the brain.
Erring on the Side of Gluttony
The discovery of each of these chemical factors in the past two decades incited lavish hopes of developing weight-loss drugs that mimic or foil their action. Yet no therapy based on the new substances has helped to harness appetite in people. When the appetite-suppressing hormone leptin was discovered by investigators at Rockefeller University in 1994, for example, it was hailed as a potential cure for obesity. Genetically modified lab rats that don't produce leptin spend all their time under the chow hopper and become grossly obese, just like the VMH-compromised rats. Maybe, the reasoning went, obese people were likewise deficient in leptin, and leptin injections would quench their appetites. The California company Amgen certainly banked on it, spending $20 million to license the leptin patent from Rockefeller.
But so far researchers have identified barely a dozen people worldwide who suffer from leptin deficiency. While they are indeed fat, the vast majority of obese people have abnormally high leptin levels—which might be expected, since the hormone is made by fat cells. Leptin therapy doesn't decrease appetite or lead to substantial weight loss in such people, or even in the merely overweight. Obesity researchers now think the brain cells of most fat people may have an insensitivity to leptin not unlike the insulin resistance that typifies Type 2 diabetes. Their bodies may be more finely tuned to detect decreases in leptin levels—reflecting a potentially life-threatening loss of body fat—than increases resulting from leptin injections or being overweight.
In light of the findings, some re-searchers wonder whether leptin's function in the appetite-regulation network has been misinterpreted. Instead of acting primarily as an appetite suppressant that induces satiety when levels are high, leptin's main role may be as a proxy for body fat, sounding the homeostatic alarm when levels start to fall. "It's not clear that leptin's role in the body is to keep us from getting fat," says Princeton psychologist Hoebel. "It's really a way of keeping us from getting too skinny."
Experiments with the appetite stimulant neuropeptide Y also suggest that the stomach-hunger system is rigged to promote appetite more than curb it. Injecting NPY into the brains of rats, for example, causes feeding frenzies, just as you'd expect. But genetically engineered rats with no NPY at all still eat plenty. Why is stomach hunger so intractable?
Obesity experts point out that, from an evolutionary perspective, overeating has until lately been more adaptive for our species than moderation. For most of its history, Homo sapiens lived a hunter-gatherer lifestyle in which supplies of food were scarce and unpredictable. "Under such conditions, the ability to ingest and store as many calories as possible when food is readily available would have obvious survival value," observes neurologist Barry E. Levin of New Jersey Medical School in Newark. Our bodies are metabolically suited to the intermittent availability of food, he explains in a recent report in the Journal of Physiology entitled "Why Some of Us Get Fat and What We Can Do About It." Cheap and easy calories are a relatively recent invention. The appetite-regulation network has evolved over millions of years to err on the side of gluttony.
Earth's First Addiction
To aid the cause of gluttony, evolution has also furnished us with a suite of neurochemicals and neural circuits that make eating a deeply pleasurable activity. We want to eat, even—often—in the absence of metabolic need. The brain-hunger system motivates and rewards eating by creating conscious sensations and impulses related to food: I like that, I want that, That was good, I want more. If your mouth waters when you pass the pastry shop after lunch, you can blame brain hunger. If you find yourself exchanging good cash for a nutritionally impaired profiterole, blame brain hunger.
And if that cream puff tastes as good as sex feels, it's no coincidence. Brain hunger emanates from some of the same neural signals and pathways that orchestrate orgasm. They include a part of the limbic system called the striatum, which helps create motivation, and the neurotransmitter dopamine, which guides pleasure seeking and produces feelings of enjoyment. "Now we're not just talking about energy balance," says Gene-Jack Wang, head of medicine at Brookhaven National Laboratory in Upton, New York. "We're talking about human psychology."
In brain-imaging studies of human subjects, Wang and Nora Volkow, director of the National Institute on Drug Abuse, have shown that the mere sight and smell of barbecued chicken, hamburgers, and pizza release dopamine in the striatum. The amount released correlates with the strength of the subjects' yearning to eat: the subjective impression I want that. "This is how our brains control our desire," says Wang.
That desire can easily get out of hand. The dopamine reward system is implicated in compulsive gambling and drug abuse, as well as in eating and sex. Consequently, Wang and other researchers have begun to suspect that obesity, eating disorders, and even the ordinary urges of appetite might resemble addiction. Bart Hoebel's studies of rat junkies show that every drop of sugar syrup they swallow causes a surge in their dopamine levels—a benchmark of desire and a biochemical marker of substance abuse.
"Boosting dopamine time after time is what drugs of abuse do," Hoebel says. "That makes you wonder whether food might have addictive properties."
Actually, it's the other way around: Drugs have addictive properties because they tap into appetite's pleasure network. Food, you might say, is the original addiction. Edibles high in fat and sugar are known to cause release of the group of feel-good chemicals known as opioids, which mask pain and promote euphoric sensations. The same brain receptors that bind the opioids released by Double Stuf Oreos also respond to morphine and heroin, with more pronounced results.
"Food gives you a modest physiological response via those pathways; drugs give you a tremendous response," says psychiatrist Walter H. Kaye, director of the eating-disorders program at the University of California, San Diego. "Drugs hijack the food-reward pathways."
So it's not surprising that food can become as much of an obsession as controlled substances. The question is how. Like human addicts, Hoebel's sugar junkies develop hypersensitive dopamine receptors that overreact to a variety of drugs of abuse, and the changes are long-term; even after a month of abstinence, the taste of sugar incites the rats to addictive behavior. Boggiano's Oreo-bingeing rats have long-term changes in their brain opioids that somehow make them unusually responsive to highly palatable foods. Even a single morsel of cookie will trigger a binge, much as a single drink can send an alcoholic on a bender. The physiology behind dopamine and opioid sensitization isn't yet clear. What's alarming for ordinary human eaters are the circumstances that create such obsession.
While extreme diets may prime the brain's reward system for bingeing behavior, researchers are finding, to their dismay, that any kind of weight-loss diet sets you up for biochemical warfare with the stomach-hunger network. The body, it seems, doesn't "know" when it's overweight; it only "knows" when it's in jeopardy of losing weight.
Weight-loss dieting, by definition, requires lowering food intake below the amount the body needs to maintain its present form. So, in a valiant attempt to regain homeostasis, the dieter's stomach-hunger system lowers levels of the satiety signals leptin and insulin and pumps the hunger hormone ghrelin into the bloodstream. Scientists still don't know how the brain- and stomach-hunger systems interact to support or override each other. What's certain is that, when you diet, you're up against your appetite's wants as well as its needs; you get clobbered with both kinds of hunger.
"A man can do what he wants, but he can't want what he wants," Schopenhauer declared. The German philosopher's grim perspective certainly applies to appetite. Between the twin imperatives of brain and stomach hunger, there doesn't seem to be much room for free will. Yet if the potency of appetite seems excessive, consider this: How many meals would you skip if you never had any cravings? The answer is probably too many. If eating were an experience as neutral as breathing, would we bother to spend hours each day shopping, cooking, and blowing our paychecks in restaurants? Or would we have to remind ourselves, every so often, to take time out for a bite—the way we often catch ourselves holding our breath, and remind ourselves to breathe?—Karen Wright
Stress Eating: Dieting Makes You Do It
Lab rats aren't bingers by nature; they have to be trained to binge by repeated cycles of food restriction and junk-food feasts. The feast-and-famine cycles look a lot like yo-yo dieting, says UAB's Mary Boggiano. She suspects that extreme dieting, combined with occasional sugar-and-fat-filled sprees, might prime a person's neurochemistry for bingeing behavior, creating the same long-term sensitization in the dopamine and opioid systems that occurs in addiction. The changes could make a person especially vulnerable to bingeing in response to stress, because stress hormones can also stimulate cravings for high-calorie comfort foods.
"Half of us overeat when we're stressed, and half undereat," Boggiano says. The people who overeat tend to be those with a history of dieting. "That's a real message. You can't prevent stress, but you can control whether or how you diet."
Diets to avoid include crash diets that severely limit calories, she says, or those that eliminate particular food groups, such as the Atkins diet. Diets that emphasize moderation and allow all food groups, such as the Weight Watchers approach, are less likely to oversensitize the brain's dopamine and opioid systems.
Whether you weigh 130 or 330 pounds, your hunger networks are engineered to defend your body's existing weight. Still, that's no cause for diet defeatism. We can still attempt to regulate weight.
- Avoid feast-and-famine eating; it fundamentally alters the body's ability to sense and respond to satiety signals. Eat regular meals.
- Eat moderately from all food groups; do not eliminate fats or carbohydrates, but don't overindulge in them, either.
- Know when you're stressed, and plan other ways to manage it besides eating.
- Minimize exposure to the sight and smell of enticing food; avoid buffet presentations of food. They trigger brain hunger that is hard to resist.
- Avoid fast-food chains; they're not only calorie-dense, they actively stimulate brain hunger, creating a double-barreled assault on regulatory mechanisms.
- Avoid gaining weight in the first place; even in obesity-prone people, prevention of weight gain through adolescence can permanently alter energy-balance mechanisms.
- If you start gaining weight, push yourself to increase energy expenditure by exercising, even though you don't feel like it.