The biology of big

There is a compelling amount of scientific evidence surrounding the biology of obesity — evidence that tells us people do not start on a level playing field when it comes to weight gain. One of the most powerful studies linking obesity to genes was done in 1994 by Jeffrey Friedman and Rudy Leibel at Rockefeller University. They were studying a mutant strain of obese mice that could not stop eating. The scientists found that the uncontrollable appetite of the obese mice was caused by a mutation in a gene that produced the hormone leptin, which acts as a satiety signal to regulate both appetite and metabolism. A few years later, a British team found that two young, morbidly obese children lacked leptin in their bodies. As it turned out, these two obese children had a rare mutation in the leptin gene, so their bodies failed to manufacture the hormone. Consequently, they were constantly hungry and ate excessively, just like the obese mice. One child, who weighed 190 pounds as an eight-year-old, was barely able to walk and had to be transported about in a wheelchair. Both children were able to dramatically reduce their food intake when doctors injected them with leptin. The hormone curbed their constant hunger, and they were eventually able to get their body weights within a normal range.

Unfortunately, leptin treatment is not a panacea for the vast majority of overweight people who are not leptin-deficient. In fact, being overweight typically signals a higher than normal supply of leptin because weight gain increases circulating levels of the hormone. People possess different sensitivities to the hormone’s satiating actions, so people who are naturally less sensitive to leptin may be predisposed to gaining weight. On the other hand, those with a high sensitivity to leptin become satiated quickly, and consequently eat less than others. Leptin sensitivity is one example of how some people are biologically disadvantaged when it comes to weight gain. The exceedingly rare genetic defect in the two children showed scientists that a single genetic mutation can dramatically affect a person’s weight. It was strong evidence that a person’s biology could have a profound impact on his or her eating behavior.

Since then, other scientific discoveries have tightened the links between biology, behavior, and obesity. In August of 2006, researchers led by Catherine Kotz of the University of Minnesota found that a chemical produced in the brain called orexin stimulated appetite and physical activity in rats. They found that obesity-prone rats —made by breeding obese rats with other obese rats — had lower levels of baseline activity and significantly lower levels of orexin gene expression than obesity-resistant rats. While the obesity-resistant rats frequently made minor movements, like standing up or grooming themselves, the obesity-prone rats did not move much at all. The results of their research showed that obesity in these rats was due to a lower level of physical activity which, in turn, was likely due to a biological difference in orexin levels. Orexin is also known to be involved in sleep disorders like insomnia — a common problem amongst the obese.

Even more recently, in April of 2007, scientists showed, for the first time, that obesity is linked to a gene common in the population. A large group of U.K. scientists, led by Andrew Hattersley of the Peninsula Medical School and Mark McCarthy of the University of Oxford, found that a specific variation in the FTO gene — present in 16 percent of the nearly 39,000 people studied — was associated with extra body fat, obesity, and type II diabetes. This was the first clear evidence that a common gene significantly increased the risk of obesity in some people. While the recent finding is important, it’s not yet known what the FTO gene does and how it predisposes individuals to obesity. Nevertheless, FTO has already been dubbed the “obesity gene,” and has added further support for the idea that obesity is a product of biology and genes, not of poor personal choice.

Leptin, orexin, and possibly FTO are all parts of a biological system of signals that tightly regulates our caloric intake and energy expenditure. These signals modulate areas of the brain, such as the hypothalamus, that control how much we eat, sleep, and move. The reason why it is difficult to lose weight and to keep it off is because these processes are all designed to resist weight changes. When our bodies detect weight loss, they produce signals to make us hungry. Getting someone to ignore these signals is like telling them to voluntarily stop breathing; they can hold their breath for some time, but eventually they will have to breathe because it’s biologically hardwired. It is these biological and genetic variations among individuals that will eventually explain why some of us gain weight easily, while others, with similar lifestyles and diets, do not. Several recent books explore the science of obesity and dieting, including Ellen Shell’s The Hungry Gene: The Science of Fat and the Future of Thin and Gina Kolata’s Rethinking Thin.

Mind over body

While science has worked to reveal the strong role of genes that predispose an individual to obesity, a person’s — and his or her genes’ — interaction with the environment are still crucial to how heavy a person will be. Unfortunately, in the recent past, America’s dietary environment has become increasingly toxic. The widespread availability of cheap, easy-to-prepare, high-fat foods coupled with increasingly sedentary work and life settings has greatly increased the number of obese in the United States, and indeed worldwide. It’s deceptively easy to eat a lot of food and then sit down for most of the day — first at the office, then at home.

Stacey Eddy is all too aware of these facts and the uphill battle she has against her own body, so she’s been taking steps to change her behavior. Her portions are now smaller, and she has changed her whole mentality towards eating. When a craving strikes for sweets, such as a candy bar, she breaks the candy bar in half and throws the other half away. Eddy explains, “I used to eat food like an addict would drink alcohol. I emotionally eat for the same reasons that someone would drink a six-pack of beer.” But now she doesn’t indulge in snacks or ice cream when it’s been an emotional day. She rewards herself with things other than food, like buying herself a new wallet when she reached 330 pounds. Another motivational strategy she uses is to set small goals for herself, like buying pants that are too small and seeing how long it takes for her to fit into them. Her pant size used to be a 42 (plus size 4X), but now she fits nicely into a size 26.

With her up-to-date knowledge about both the physiology and the psychology of obesity, Eddy is using her mind and will to shape her new body. She has already lost over 110 pounds from her maximum weight, and is steadily making progress toward her target of 150 pounds. Her story is an example of how people who are predisposed to obesity can learn to manage their bodies and rein in the genes that nature gave them. When Eddy was over 400 pounds, she could not imagine what being 300 pounds would feel like. Now that she is almost 300 pounds, she can start to see herself at 200. She hasn’t been less than 300 pounds since the sixth grade. Someday soon, her bus rides will be a whole new experience.

Eric Hau-Yun Chang