Genes Take Charge, and Diets Fall by the Wayside

From the New York Times:

Fred R. Conrad/The New York Times

It was 1959. Jules Hirsch, a research physician at Rockefeller University, had gotten curious about weight loss in the obese. He was about to start a simple experiment that would change forever the way scientists think about fat.

Jules Hirsch, a research physician at Rockefeller University, conducted a simple but groundbreaking experiment on obesity nearly 50 years ago, changing the way scientists think about fat.

Obese people, he knew, had huge fat cells, stuffed with glistening yellow fat. What happened to those cells when people lost weight, he wondered. Did they shrink or did they go away? He decided to find out.

It seemed straightforward. Dr. Hirsch found eight people who had been fat since childhood or adolescence and who agreed to live at the Rockefeller University Hospital for eight months while scientists would control their diets, make them lose weight and then examine their fat cells.

The study was rigorous and demanding. It began with an agonizing four weeks of a maintenance diet that assessed the subjects’ metabolism and caloric needs. Then the diet began. The only food permitted was a liquid formula providing 600 calories a day, a regimen that guaranteed they would lose weight. Finally, the subjects spent another four weeks on a diet that maintained them at their new weights, 100 pounds lower than their initial weights, on average.

Dr. Hirsch answered his original question — the subjects’ fat cells had shrunk and were now normal in size. And everyone, including Dr. Hirsch, assumed that the subjects would leave the hospital permanently thinner.

That did not happen. Instead, Dr. Hirsch says, “they all regained.” He was horrified. The study subjects certainly wanted to be thin, so what went wrong? Maybe, he thought, they had some deep-seated psychological need to be fat.

So Dr. Hirsch and his colleagues, including Dr. Rudolph L. Leibel, who is now at Columbia University, repeated the experiment and repeated it again. Every time the result was the same. The weight, so painstakingly lost, came right back. But since this was a research study, the investigators were also measuring metabolic changes, psychiatric conditions, body temperature and pulse. And that led them to a surprising conclusion: fat people who lost large amounts of weight might look like someone who was never fat, but they were very different. In fact, by every metabolic measurement, they seemed like people who were starving.

Before the diet began, the fat subjects’ metabolism was normal — the number of calories burned per square meter of body surface was no different from that of people who had never been fat. But when they lost weight, they were burning as much as 24 percent fewer calories per square meter of their surface area than the calories consumed by those who were naturally thin.

The Rockefeller subjects also had a psychiatric syndrome, called semi-starvation neurosis, which had been noticed before in people of normal weight who had been starved. They dreamed of food, they fantasized about food or about breaking their diet. They were anxious and depressed; some had thoughts of suicide. They secreted food in their rooms. And they binged.

The Rockefeller researchers explained their observations in one of their papers: “It is entirely possible that weight reduction, instead of resulting in a normal state for obese patients, results in an abnormal state resembling that of starved nonobese individuals.”

Eventually, more than 50 people lived at the hospital and lost weight, and every one had physical and psychological signs of starvation. There were a very few who did not get fat again, but they made staying thin their life’s work, becoming Weight Watchers lecturers, for example, and, always, counting calories and maintaining themselves in a permanent state of starvation.
“Did those who stayed thin simply have more willpower?” Dr. Hirsch asked. “In a funny way, they did.”

One way to interpret Dr. Hirsch and Dr. Leibel’s studies would be to propose that once a person got fat, the body would adjust, making it hopeless to lose weight and keep it off. The issue was important, because if getting fat was the problem, there might be a solution to the obesity epidemic: convince people that any weight gain was a step toward an irreversible condition that they most definitely did not want to have.

But another group of studies showed that that hypothesis, too, was wrong.

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