It seems so simple: Too much food and too little activity make people fat. But the actual processes that create and perpetuate that imbalance are proving to be astoundingly complex.
Biology, physiology, psychology, genetics and environment figure in the obesity equation to varying degrees. Scientists are trying to understand how, in recent decades, the population has bloated to a point that lean people are a minority.
"There is no simple answer," said Bernard Fuemmeler, a Duke University researcher who is studying the mind-body link in obesity. "People tend to think that it may be willpower or just a lack of control. And these may be reasons, but not explanations for what is driving the epidemic."
In their quest for explanations, researchers at Duke, UNC-Chapel Hill, Wake Forest and East Carolina universities are discovering or building upon findings that prove just how intractable a foe fat can be:
Rich foods work much like heroin on the brain, making it hard to stop eating them. A recent study indicates a genetic link between overeating and drug addiction, explaining why obese people have such intense cravings and build up such tolerance.
Depression and obesity can be so tightly linked, it's hard to tell which comes first. Some of the same hormones and neurotransmitters are active in both, which could explain a tendency to eat when not hungry.
And as people gain weight earlier in life, they not only get chronic diseases sooner, they also set the course for a lifetime of weight battles. Growing evidence points to biological changes in obese people that mean they must work harder to keep weight off than those who never gained.
A changing food environment
The consequences are huge. Obesity is estimated to directly kill 112,000 people a year in the United States and to contribute to the deaths of many hundreds of thousands more. Health costs associated with the epidemic are tabbed at $147 billion a year, according to an analysis by RTI International.
"We evolved from species that have lived for the last millions and millions of years in environments in which food was hard to come by," said Wayne Pratt, a behavioral psychologist at Wake Forest University who has explored the connection between food and addiction. "And the food environment has changed in the last 50 years."
Those changes — cheap, abundant and tasty food that requires almost no physical effort to obtain — have upset an intricate equilibrium within the body that is at the very essence of existence.
Food is life; every system in the body depends on it. But too much of anything, even a basic necessity, can create a poison.
Well-educated and motivated, Jennifer Joyner began every day determined to lose weight. By noon, she was off course.
"I used that failure to go ahead and eat (poorly) the rest of the day," said Joyner, 38, who lives in Fayetteville, N.C., with her husband and two children. At her heaviest, she carried 336 pounds on her 5-foot-5-inch frame.
Joyner firmly believes she was addicted to food.
"Nobody is that heavy because they don't know how many calories they should limit themselves to," Joyner said. "That's absurd."
Pleasure centers in the brain
There's growing evidence she might have a case.
High-energy foods hit the same pleasure centers of the brain that heroin and cocaine activate, recent research has found. Wake Forest's Pratt said that very brain circuitry was once an evolutionary benefit.
Humans were programmed to like sweets and fatty foods so they'd eat more of them during those fleeting moments of abundance — finding a berry bush or a trove of tree nuts.
"It makes sense to eat more than you'd need for that day, so you could put down a layer of fat to survive" during the inevitable periods of scarcity, Pratt said. "The reward system is there to take advantage of things that are beneficial to us."
Even though people are hard-wired to find rich foods pleasurable, most are not addicted in the sense of becoming increasingly compulsive and self-destructive.
But in an unprecedented environment of food abundance, a steady diet of cheeseburgers, pizzas and doughnuts can trigger in some the same cravings and tolerances that an addict gets from heroin or cocaine. Recent brain studies show that drug addicts and people who are obese have similar neurobiological circuitry.
Studies with rats show why we start craving fat. Rats on high fat and sugar diets begin craving the foods because the reward centers in their brains grow numb to the pleasure signals, much like the addict develops a tolerance to cocaine that fuels more and bigger binges. As a result, the rats eat more and more, growing obese.
Adding to the biological evidence, a team of scientists that included UNC-Chapel Hill researchers reported in 2009 that they had found a gene, NRXN3, associated with obesity in some people. The same gene previously was identified as playing a role in substance abuse.
Keri Monda, an epidemiologist at the UNC Gillings School of Global Public Health and one of the study's authors, said the finding draws a strong inherited link between overeating and drug addiction — problems characterized by difficulties limiting enjoyable experiences.
"We do know there are common underpinnings," Monda said, adding that additional studies are needed to make a definitive association.
For Joyner, the science only confirms her experience. In March 2008, she had weight-loss surgery and has since dropped 150 pounds and written a book about her experience, "Designated Fat Girl." But overcoming her addiction, she said, has taken counseling and work beyond the operation.
"You don't treat addiction with a diet-and-exercise plan," she said. "There needs to be intervention, family support, ongoing counseling."
As anyone who has battled obesity knows, the struggle is as much mental as physical. Sadness, self-loathing, disgust and frustration often accompany weight gain. Bad health begets a bad frame of mind, which begets more bad health.
The connection between depression and obesity, long linked by the anecdotal experiences of people who suffer from both, is only recently becoming better understood. Some of the same hormones and neurotransmitters are active in both diseases.
Fuemmeler, the Duke researcher, was the lead author of a 2009 study that investigated the intersection of depression and obesity.
It's a confounding area of research.
"There is some controversy about the relationship between obesity and depression," Fuemmeler said, noting that many factors cause depression and that an equal number cause obesity. Often, the two overlap, and it's hard to determine whether one causes the other.
Fuemmeler said his colleagues are studying brain chemicals that regulate reward and mood.
"These biobehavioral mechanisms might be driving both depression and/or a tendency to eat when not hungry," he said.