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Observations on obesity

By Tim Stoddard

Obesity has quietly emerged in the past two decades as a disease of pandemic proportions. Once considered the incarnation of gluttony and sloth, obesity has recently been revealed as a disease with biological and environmental roots. In her new book, The Hungry Gene: The Science of Fat and the Future of Thin (Atlantic Monthly Press, 2002), Ellen Ruppel Shell offers the first comprehensive look at the arc of the obesity epidemic and what we can do about it.

Ellen Ruppel Shell Photo by Kalman Zabarsky


Ellen Ruppel Shell Photo by Kalman Zabarsky


Shell, a COM associate professor of journalism and codirector of COM’s Knight Center for Science and Medical Journalism, admits that until recently she had not thought of obesity as a disease. “Like everyone else,” she says, “obesity had always been a gestalt for me. I thought of it as an eating disorder, a psychological problem.”

Her perception of obesity took an about-face in the late 1990s when she met with the chief business officer at Millennium Pharmaceuticals, a biotechnology firm in Cambridge, Mass. A medical correspondent for The Atlantic Monthly, Shell wanted to learn more about how the recently sequenced human genome would improve the discovery of drug targets. She asked the guru at Millennium a straightforward question: if he could dedicate all his company’s resources to a single disease, which one would it be? His answer was neither cancer nor heart disease.

It was obesity.
Americans spend $33 billion a year on diet schemes, health clubs, and weight loss medications. And yet, Shell says, we are getting fatter. For much of the 20th century, the percentage of obese Americans remained a steady 13 percent. Then in the 1980s it shot up to 21 percent and has continued to climb. Recent data from the Centers for Disease Control indicate that 31 percent of Americans are now obese and that 65 percent are overweight.
Obesity-linked heart disease is currently the number two public health risk, killing 300,000 Americans annually. But last December, former U.S. Surgeon General David Satcher predicted that within the next decade obesity will eclipse tobacco as the leading cause of preventable deaths.

Americans are not the only victims. As Shell discusses in her book, half the adult populations of Brazil, Chile, Colombia, Peru, England, Finland, and Russia are overweight or obese. In China, where obesity was virtually unknown until the introduction of a high-fat, Western-style diet, obesity has increased sixfold in the past 10 years.

Of hungry mice and men
In the 1990s, two key discoveries revealed the deep genetic roots of obesity. Researchers had long suspected that mice, and perhaps humans, produce a hormone in their fat cells that acts as a satiety signal. At Rockefeller University, molecular biologists Jeffrey Friedman and Rudy Leibel had been searching for the elusive hormone in a mutant strain of obese mice since the 1970s. These corpulent rodents couldn’t stop eating, and the scientists believed that their gluttony was caused by a mutation in the genes that regulate appetite.

Without knowing what the hormone was or where it was found in the mice, Leibel and Friedman embarked on what Shell calls a technical tour de force. “Their work was an amazing piece of science,” she says. “It was like trying to find a long-lost uncle somewhere in the United States -- you don’t know what he does, you don’t know what he looks like. They had this massive territory in which to look for a tiny speck.” Friedman named the hormone leptin (from the Greek leptos, for thin), and for three years following its 1994 discovery, researchers scrambled to find its corollary in humans.

A British team finally found the leptin gene in two obese young cousins whose hyperphasia, or excessive eating, had baffled specialists for years. Because of an exceedingly rare mutation, the children did not manufacture leptin, which meant that their hunger switch was continously turned on. The children were healthy, except for their size and their voracious hunger. The older child, an eight-year-old girl who weighed 190 pounds, could no longer walk, and was transported about in a wheelchair. The two-year-old was 65 pounds. Leptin injections immediately curbed their appetites, however, and the kids stopped begging for food and no longer scavenged for scraps in the trash or pilfered frozen fish sticks from the freezer. The girl lost 30 pounds in a year and was soon walking without assistance. Her younger cousin showed similar improvement.

The Hungry Gene by Ellen Ruppel Shell

Leptin was a miracle drug for these children, but only about a dozen people worldwide have been found to have the rare leptin mutation. Most overweight people are not leptin-deficient at all. They have plenty of the hormone, which is produced by fat cells, and may in fact be resistant to their own leptin, much as people susceptible to diabetes can become insensitive to their own insulin. After all the hype over the leptin discovery, it has not panned out as the antiobesity panacea that pharmaceutical companies slavered over in 1994. But as Shell writes, the discovery “had shown that a tiny defect in a single gene could have a profound impact on human behavior. The treatment made inescapable that the drive to overeat has deep genetic roots.”

When Micronesians became Macronesians
An inclination toward obesity may be written in the genes, but it is the environment that has caused the pandemic. The world, Shell says, has become increasingly obesogenic. Nowhere is this more evident than on Kosrae, a tiny Micronesian island of 8,000 inhabitants that Shell visited with an American epidemiologist. Over 80 percent of the adults on Kosrae
are obese, and the population dies young. “The big killer of adults on Kosrae,” Shell writes, “is what epidemiologists call the ‘New World Syndrome,’ a constellation of maladies brought on not by microbes or parasites, but by the brutish assault of rapid westernization on an unassuming traditional culture.” Kosraeans no longer eat fish pulled from the sea or the bountiful bananas, breadfruit, papayas, and coconuts on their island. Their stores are stocked instead with sweet and fatty imports such as Spam and sugary breakfast cereals.

In many ways, Shell says, Kosrae is a microcosm for the larger obesity pandemic. Melanesians settled Kosrae early in the first millennium, and have developed a distinct genetic heritage during thousands of years of isolation. Like many native peoples, Kosraeans exhibit what geneticist James Neel describes as a “thrifty genotype,” a genetic makeup that encourages the conversion of calories into body fat. Neel hypothesizes that thrifty genes were necessary for indigenous peoples to survive during periods of extreme stress and scarcity. Only those individuals who managed to fatten themselves in advance of lean times could survive and pass on their genes to subsequent generations. When cooking oil, fatty meats, and processed starches arrived on the island, most adults grew fat.

“Kosrae is a dramatic example of how the United States continues to export ill health around the world,” Shell says. “The nutrition transition in Kosrae reveals how we’re affecting other cultures’ health, wittingly or not, just as the conquistadors did in the New World. This little island is a microcosm that demonstrates the larger point.”

Look homeward, angel cake
In affluent America the environment has become obesogenic in other ways. It’s no surprise that fast food outlets have substantially increased the sugar and fat in their offerings. For a public inured to drive-thrus and super-sized meals, this is not news. But Shell’s analysis of Big Food offers a fresh look at why we are eating sweeter and fattier foods. The trick to selling unhealthy food, she says, is to enlist children as lobbyists. “The kids’ market is the conduit to the entire food market,” she says. “Kids are now very powerful ambassadors for the family in terms of food purchases, much more so than a generation ago. In many cultures, children outgrow these innate preferences, but in America, because children are so important in how we buy food, we do not outgrow those preferences.”

The key to reversing the obesity epidemic, Shell says, is not pharmaceutical. “I’m not championing drug treatment as a solution to obesity,” she says. “The discovery of leptin has galvanized the field and people are now looking more closely at the mechanisms that drive eating and appetite, but controlling those behaviors is extremely difficult. The idea that we would medicate the majority of the population is not a particularly hopeful one.”

Instead, Shell outlines several ways to disarm the obesogenic environment. For starters, Americans should relieve the U.S. Department of Agriculture of the paradoxical task of both promoting American food and advising the public on nutrition. “It’s really the USDA’s job to encourage us to buy American products, and you can’t do that and also tell the public what they really need to hear, which is that we need to eat less,” she says.

It’s also time for the U.S. government to boost its chronically underfunded obesity prevention programs, she says. Since 1980, when “responsible eating” and “healthful behaviors” became explicit goals of national health policy, the total budget for obesity programs has been less than $9 million. In contrast, Shell says, the initial phase of a new campaign to sell the Milky Way candy bar is $25 million a year. “We need to balance that kind of advertising pressure with some messages that are as powerful as the ones that the food companies are putting forward. I’m not castigating the food industry. They’re in the business to make money and satisfy shareholders. But we’re supposed to be a compassionate society, so given that our environment already inflicts this disease on such a large number of people, and children in particular, maybe we ought to think of adjusting the environment.”

Boston University researchers are shedding light on the complex causes of obesity, its health consequences, and better treatment options. For more information on these endeavors, please visit the Web site of the Obesity Research Center at http://medicine.bu.edu/orc.

When Friedman’s group finally isolated leptin and the gene that codes for it, the news was an overnight sensation. The drug giant Amgen bought the rights to leptin for an astonishing $20 million upfront, reportedly the largest amount ever paid for a university-held patent. In the years since then, the promise of leptin has dimmed. Researchers now know that leptin is not very good at preventing normal people from eating too much, because its primary role is not to keep us from getting fat, but to keep us from getting too thin. A radical fall in leptin induces a starvation response that increases appetite, but a boost of leptin does not make us feel full.

It may be that leptin is required for people to be satisfied, but that leptin alone is not enough.

Indexing the Body

Physicians assess overweight with the body mass index (BMI), which is calculated by dividing weight in kilograms by height in meters squared.
A person with a BMI over 25 is overweight. A BMI over 30 qualifies as obese. A five-foot, five-inch woman weighing 180 pounds has a BMI of 30, as does a six-foot, two-inch man with a weight of 233 pounds. A team of BU researchers has recently investigated the relation between BMI and heart failure, a chronic condition in which the heart’s ability to pump blood is impaired. The doctors examined the records of 5,881 participants in the Framingham Heart Study, the National Heart, Lung, and Blood Institute’s landmark epidemiological study operated by BU, and found that obesity was singularly responsible for doubling the risk of heart failure. For every increase of 1.0 on the BMI, the researchers say, the risk of heart failure increased 7 percent for women and 5 percent for men.

1 November 2002
Boston University
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