CURRENT ISSUE

SUBSCRIBE

CONTACT US

ADVERTISING

SEARCH

BACK ISSUES

CONTRIBUTORS'
GUIDELINES

THIS WEEK IN
CALIFORNIA WILD

Counterpoints in Science

Globularization

Jerold M. Lowenstein

Lately, Ive read a steady stream of scientific and popular articles about the epidemic of obesity sweeping America. Obesity is a big subject, with evolutionary, genetic, biochemical, and cultural components. And it affects us all, directly or indirectly. In my job as chairman of the department of nuclear medicine at California Pacific Medical Center, Ive observed increasing numbers of overweight patients. Obesity is a problem that frustrates both patients and physicians.

In order to undergo nuclear scans, patients have to lie on a table above or below an imaging device. Until a few years ago, we used tables that would support a maximum of 250 pounds and rarely had patients too heavy for them. But as the number of patients who couldnt use the tables began to swell, we got a table that could handle 350 pounds without breaking. Before long, though, we were turning away patients and had to acquire a table capable of carrying 400 pounds. In the past year, weve had several individuals too hefty even for that platform.

The latest national statistic indicates that 55 percent of Americans are overweight and 20 percent are obese, that is, exceed the norm by 30 percent or more. Some fat rights advocates were quoted recently in the San Francisco Chronicle as maintaining that being fat is natural for some people and not unhealthy. But diabetes, hypertension, heart disease, breathing problems, cancer, blood clots in the veins and lungs, infertility, and arthritis, among other disorders, are much more common in the obese than in those of normal weight, regardless of their body build.

Although no one knows why the risk of breast, colon, and other cancers increases with obesity, some conditions connection to excess weight are understood. For example, the extra load of fat depletes the insulin supply, causing diabetes, absorbs female hormones necessary for fertility, and stresses the heart, blood vessels, lungs, and joints. Conditions related to obesity are estimated to cause 300,000 premature deaths annually in the United States, forming a countercurrent to the general trend of increasing longevity.

Indeed, our nuclear scans are often directed toward diagnosing diseases related to being overweight. One day last week, we did a heart scan on a 410-pound man who came to the emergency room with chest pain. That same night I was called in for another emergency, a lung scan on a 430-pound woman with severe shortness of breath. In both cases, we had to image the patients sitting up, since they were too heavy for the table. The picture quality suffered, from the upright position and from the obscuring layer of fatty tissue, but the images were fortunately good enough to show that the man was not having a heart attack and the woman did not have potentially lethal pulmonary emboli (blood clots in the lung).

How can we account for this phenomenal growth in avoirdupois, which seems to be rising with the gross national product? What, if anything, can be done about it?

From the evolutionary point of view, an obese population of humans is an anomaly, made possible by surplus food and labor-saving devices. Body weight depends on the difference between calories of food taken in minus calories of heat and energy expended. During 99 percent of human history, our ancestors lived as hunter-gatherers. They walked several miles a day foraging for food. They expended tremendous energy for a barely adequate intake of calories. A fat person, if one existed, would not have kept up with the group and would have perished. On the other hand, it was certainly advantageous to put on some weight when food was abundant, to resist death by starvation in times of famine.

Natural selection didnt prepare us for our present living conditions, surrounded by fast food outlets and tuned in to TV ads exhorting us to consume shakes, burgers, and fries. Americans are eating more of these high-fat, high-calorie foods, while watching more hours of TV. Meanwhile, we take elevators rather than walk up or down two flights of stairs. We drive to work and to the grocery store. An overweight friend even drives his suv six blocks to the gym to work out. Post-industrial society offers the mass of humanity, for the first time in our five-million-year saga, the opportunity to eat much more and exercise much less than is good for us.

The United States has the highest proportion of overweight and obese individuals, but the rest of the world is catching up fast. Europe is heavy on our heels, and even the developing world is encountering more and more the maladies of excess. Hard as it is to believe, according to Peter G. Kopelman of the Royal London School of Medicine, writing last April in the journal Nature, obesity has become so common within the worlds population, it is replacing undernutrition and infectious diseases as the most significant contributor to ill health.

How do we know if were overweight? The most practical measure is the body mass index (BMI), ones weight in kilograms divided by the square of ones height in meters. A normal BMI usually ranges from 18.5 to 24.9, overweight from 25 to 29.9, obese from 30 to 39.9, morbid obesity as more than 40. There is a U-shaped relationship between mortality and BMI, with the death rate increasing among people with BMIs below 18.5 or above 24.9. The underweight limb of the curve consists mostly of smokers and those who have lost weight from an unrecognized, eventually fatal illness. As the BMI rises above 24.9, the relative risk of diabetes, gallstones, hypertension, and coronary heart disease increases with it.

Everyone has an opinion about how to control weight, but opinion is not science. The prevailing idea that diet and self-discipline will take care of the problem constitutes a very expensive delusion. The American diet industry takes in 50 billion dollars annually, but 95 percent of those who go on any particular diet find themselves at or above their starting weight a year later.

As a practicing endocrinologist, I treated many patients for their “weight problem,” which they hopefully, and usually erroneously, attributed to a hormonal imbalance. My experience was the same as that of other practitioners: On any diet and exercise regimen, patients lost weight initially, but within a few months the vast majority had gained it all back. Those few who stick with a program, almost any program, lose weight and keep it off. But chronic food restriction and regular exercise are too difficult for most. Its easier to go seek new diets and new weight-loss gurus and go through the cycle again and again.

Clearly, powerful physiological mechanisms obstruct our attempts to lose weight. Five years ago, the discovery of leptin promised a big breakthrough in understanding these mechanisms. When leptin, an appetite-suppressing protein absent in a certain strain of obese mice, was injected into these fat mice, they lost half their excess weight within a month. Leptin—in mice, men, and other mammals—is secreted by fat cells; the more fat cells, the more leptin. Leptin acts on the brains hypothalamus to turn off some of the nerve signals that increase appetite. Its a feedback control that tells an individual when he or she is too fat and switches off the appestat. There was great excitement and hope that leptin would turn out to be the wonder drug for the overweight.

Unfortunately, what works in mice doesnt always work in humans. Unlike mice, most obese people do not lack leptin. On the contrary, they have higher levels than normal. Mice with high leptin levels eat less, but many people with high leptin levels just keep on eating. They are like a house with a faulty thermostat thats already too hot and only gets hotter.

The pharmaceutical company Amgen of Thousand Oaks, California, paid 20 million dollars for commercial rights to leptin and tested it in obese volunteers. Leptin has to be injected, and almost half of the volunteers dropped out because the injections induced skin irritation and swelling. Those who received leptin, rather than a placebo, did average about a 15-pound weight loss. But the results were inconsistent, with some volunteers gaining as much as ten pounds. Its pretty clear that leptin is not the magic bullet against “globularization.”

If leptin deficiency and willpower deficiency are not the root causes of obesity, what is? Why, given similar circumstances, are some people fat and others lean?

Studies of twins, especially identical twins separated early in life, indicate that genetic factors largely determine the odds of obesity. Susceptibility is not the same thing as inevitability, and cultural factors also play an important role. The prevalence of obesity in Sweden, for instance, is less than half that in the United States. In developed nations obesity is more prevalent in poorer segments of society than among the rich, who tend to be obsessed by fitness and leanness. In developing nations, where excess weight may be considered a sign of success, the richer are also fatter.

The disconnect between the reality of epidemic obesity and the svelte ideal is brought home to me in the supermarket, where I see chubby citizens loading up their shopping carts against a backdrop of magazine racks displaying skinny models. On planes these days, the seats seem to be designed for Twiggy, while our seat-mates are more likely to be of Sidney Greenstreet dimensions. The marked increase in obesity in children and adolescents does them no favors, healthwise and otherwise. Fat youngsters are much more likely to become fat in middleage and, unless they beat the odds, fat oldsters.

Were facing a challenge that hasnt come up before in the history of our species, so we have no precedent to guide us. There are not only more of us than ever before, there is more, on average, of each of us. Will Americans keep getting fatter until the longevity graph takes its first downturn in a hundred years? Or will the multitude of researchers looking for that golden bullet (and a billion dollars worth of stock options) succeed in slaying the fraudulent diet mavens? I just hope that my body mass index will keep me going long enough to find out.


Jerold M. Lowenstein is professor of medicine at the University of California at San Francisco and chairman of the Department of Nuclear Medicine at California Pacific Medical Center in San Francisco. jlowen@itsa.ucsf.edu

Fall 2000

Vol. 53:4