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 across North Carolina and beyond 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 are 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 means they must work harder to keep weight off than those who never gained.

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.

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