Why Are We Still So Fat?
Only bariatric surgery reliably leads to long-term weight loss. Now scientists hope to duplicate the effects with a pill.
Whenever I see a photo from the 1960s or 1970s, I am startled.
It's not the clothes. It's not the hair. It's the bodies. So many people were skinny.
In 1976, 15 percent of American adults were obese. Now it's nearly 40 percent. No one really knows why bodies have changed so much.
Scientists do a lot of hand-waving about our "obesogenic environment" and point to favorite culprits: the abundance of cheap fast foods and snacks; food companies making products so tasty they are addictive; larger serving sizes; the tendency to graze all day.
Whatever the combination of factors at work, something about the enviroment is making many people as fat as their genetic makeup permits. Obesity has always been with us, but never has it been so common.
Evreryone - from doctors to drug companies, from public health officials to overweight people themselves - would love to see a cure, a treatment that brings weight to normal and keeps it there. Why hasn't anyone discovered one?
It's not for lack of trying.
Yes, some individuals have managed to go from fat to thin with diets and exercise, and have kept off the weight. But they are the rare exceptions. Most spend years dieting and regaining, dieting and regaining, in a fruitless, frustrating cycle.
There is just one almost uniformly effective treatment, and it is woefully underused: only about one percent of the 24 million American adults who are eligible get the procedure.
That treatment is bariatric surgery, a drastic operation that turns the stomach into a tiny pouch and, in one version, also reroutes the intestines. Most who have it lose significant amounts of weight - but many of them remain overweight, or even obese.
Their health usually improves anyway. Many with diabetes no longer need insulin. Cholesterol and blood pressure levels tend to fall. Sleep apnea disappears. Backs, hips and knees stop aching.
There are not nearly enough surgeons or facilities to operate on all the obese people who might be helped by bariatric surgery, noted Randy Seeley, director of the nutrition research center at the University of Michigan.
And many patients and doctors persist in thinking - all evidence to the contrary - that if overweight people really set their minds to it, they could get thin and stay thin.
Scientists got an unsparing look at what they were up against 50 years ago, when a clinical researcher at Rockefeller University, Dr. Jules Hirsch, did some old-fashioned experiments. He recruited obese people to stay at the hospital and subsist on a 600-calorie a day liquid diet until they reached normal weight.
The subjects lost 100 pounds on average, and they were thrilled. But as soon as they left the hospital, the poinds piled back on.
Dr. Hirsch and Dr. Rudy Leibel, now at Columbia University, repeated the study again and again, with the same result. Eventually, they found that when a very fat person diets down to a normal weight, he or she physiologically comes to resemble a starving person, craving food with an avidity that is hard to imagine.
The lesson never really penetrated the popular consciouness. Just a couple of years ago, Kevin Hall, a senior investigator at the National Institute of Diabetes and Digestive and Kidney Diseases, made headlines with a study of contestants from the Biggest Loser Television show. They lost enourmous amount of weight, he found, but rarely could keep it off.
Obesity's genetic connection was conclusively demonstrated in the 1980s in a series of papers showing that body weight is strongly inherited, almost as strongly as height. Children adopted as infants ended up with weights like those of their biological parents. Twins reared apart ended up with nearly identical body weights.
It was beginning to look hopeless for obese people.
Then, in 1995, Dr. Jeffrey Friedman of Rockefeller University discovered what looked like the equivalent of insulin for diabetes - a molecule he called leptin that is secreted by fat cells and tells the brain how much fat the body has.
Leptin signals some sort of master controller in the brain. If a person is too thin - according to what the brain perceives as an acceptable weight - the brain signals that person to eat.
In fat people, that controller is set too high: their brains make sure they stay fat.
The drug company Amgen paid Rockefeller and Dr. Friedman $20 million for rights to leptin, hoping to develop it as an obesity treatment. The idea was to give leptin to obese patients so their brains would think they had too much fat.
If it worked, they ought to lose their appetites and drop pounds. By tailoring leptin injections, doctors might even fine-tune a person's weight.
To everyone's chagrin, leptin fizzled. Most people did not respond to leptin injections by losing weight. But leptin was a key to unlocking a complex network of hromones and brain signals that control body weight.
The problem was that no single target seemd to make much difference in wieght loss.
"I think of eating as a survival mechanism," said Dr. John Amatruda, a consultant and former executive at Bayer and Merck while trying to develop weight-loss drugs. "You need to eat, so our bodies are wired to have complex systems that are redundant."
The hope now is to figure out how to have the benefits of bariatric surgery without the surgery. The operation alters the body's ochestra of hormones and signals, among them leptin but also many others.
Afterward, tastes change. Many patients no longer crave the high-calorie foods that used to sate them. Many find they are no longer ravenously hungry.
Might those effects be mimicked with a drug? Many researchers are trying, although must drug companies have dropped out of the obesity market, seeing no truly effective treatments on the horizon.
Even when drugs have been approved, they are rarely used. That's not surprising, Dr. Amatruda said, because obesity medications on the market are either minimally effective for most people or have significant side effects - or both.
Dr. Seeley remains optimistic that a drug will be found. He studies mice and rats, giving them bariatric surgery and trying to untangle the web of biochemical changes that follow.
"We think we have good clues," he said," but nothing is far enough along."
For now, researchers wish people - including fat people themselves - would stop blaming the obese for their problem.
"This idea that people should eat less and exercise more - if only it were so simple," Dr. Hall said.
Nov. 19, 2018
The New York Times