Obesity, not so long ago an issue of personal struggle with fatty foods and bulging waistline, has of late become Public Health Enemy No. 1, blamed for almost a third of the rise in healthcare spending. Overeaters now find themselves in the same category as smokers or drug addicts, tainted with the aura of moral weakness and lack of willpower. This perspective has begun to spawn tough-love policies geared to prod people into thinness. Discriminating against the chubby in social and even employment settings seems to be gaining on the politically correct scale. And levying a "sin tax" on sweet treats, starting with sugary sodas and fruit juices, has a growing following on Capitol Hill.
The sharpened focus on fatness isn't surprising: Overweight is far more pervasive than either smoking or addiction, affecting over 65 percent of the population, and true obesity has more than doubled since 1980, at a cost estimated at more than a hundred billion dollars a year. The obese have shorter lives and face more diabetes, heart disease, stroke, and cancer than the thin, not to speak of the psychological burden and often lowered self-esteem. But using blame and punishment to inspire willpower and discipline in citizens to curb their appetite, eat more fruits and vegetables, and exercise more is not likely to work. Why? Because it does not begin to take into account the biological complexity of obesity and the enormous biological differences among individuals that make weight loss a snap for some and a near impossibility for others.
[Photos: states where obesity rates are highest.]
It's no coincidence that weight problems run in families. In fact, the strongest determinants of body weight and body type are found in the DNA. As convenient as it would be, however, there seems to be no single responsible gene. The closest to that is the gene that makes the hormone leptin, discovered some 15 years ago by Jeffrey Friedman at the Rockefeller University. Named after the Greek word leptos, meaning thin, the hormone is secreted by fat cells to signal the hunger center deep in the brain to suppress appetite when fat reserves are plentiful. Without leptin, animals and humans become massively obese—and the weight melts away promptly with a synthetic dose of the compound.
But surprisingly, only 10 percent of seriously obese patients have low leptin levels; for them a dose of leptin works like a charm. Most obese people have high levels of leptin. For some reason, their brain's hunger center appears resistant to leptin's signal to stop eating, so more is pumped out. This discovery inspired the identification of a multitude of other fatness-related genes and biochemical networks that shoot signals between the gut, stored fat, and the brain. The goal: to uncover the molecules or pathways that will lead to drugs able to do for weight loss what statins have done for lowering cholesterol. But that is a long way away.
The interaction of genes that predispose people to be overweight or obese with a host of environmental triggers just adds to the complexity. Genes don't change in a few decades, but environments do—and this interplay, while poorly understood, must account for the huge rise in obesity in both adults and children over the past 30 years. The star environmental players: diet and physical activity. Dietary composition, including different forms of fats and sugars, can alter gene expression and change patterns of eating and fat accumulation, for the good or the bad. Look at our children, who have also been swept up in the obesity epidemic. Heavy mothers have heavier offspring because the young ones' genetic makeup interacts with an unhealthful environment, even before birth. An overweight mother with diabetes delivers an oversugared, oversize baby set up for metabolic and weight disorders later in life. But genetic heritage can be modified by how we eat and how we live, not in bursts but in the long run.
Reversing a sedentary lifestyle can help counter fatness susceptibility. Physical activity burns up calories, curbs appetite in the overweight, limits the risk of regaining lost pounds—and can modify gene behavior. Studies have shown that regular exercise overrides the weight gain associated with carrying a variant of FTO, an obesity gene. If one needs more evidence that gene-environment interactions are part of the obesity crisis, look at the side effects of certain antidepressants and antipsychotic medicines: excessive weight gain. Susceptibility to this effect has been tied to the drugs' interactions with a number of specific genes. As a side note, if fatness can be predictably induced by drugs, there is every reason to believe that new drugs to bring the opposite effect are on the horizon. We need them to augment—not supplant—lifestyle changes.