Every year, whether you are fat or thin, whether you lose weight or gain, 10 percent of your fat cells die. And every year, those cells that die are replaced with new fat cells, researchers in Sweden reported Sunday.
The result is that the total number of fat cells in the body remains the same, year after year throughout adulthood. Losing or gaining weight affects only the amount of fat stored in the cells, not the number of cells.
The finding was published online Sunday in the journal Nature.
Obesity investigators say the study raises tantalizing questions: What determines how many fat cells are in a person’s body? When is that number determined? Is there a way to intervene so people end up with fewer fat cells when they reach adulthood? And could obesity be treated by making fat cells die faster than they are born?
“This is a new way of looking at obesity,” said Dr. Lester Salans, an obesity researcher and emeritus professor at Mount Sinai School of Medicine.
But for now, researchers say, they do not have a clue about how to answer those questions.
“There is a system waiting to be discovered,” said Dr. Jeffrey S. Flier, an obesity researcher and dean of Harvard Medical School.
He and other obesity researchers cautioned, though, that even if scientists knew how the fat cell system worked, it is not clear that it would be safe or effective to treat obesity by intervening. One of the hard lessons of the past couple of decades has been that the body has redundant controls to maintain weight.
“I suspect that the body’s regulation of weight is so complex that if you intervene at this site, something else is going to happen to neutralize this intervention,” Dr. Salans said.
But the discovery is also leading to new ways to address other questions about obesity. For example, what happens to people who are thin until adulthood and then gain a lot of weight? The study focused on people who had been fat since childhood, the usual route for adult obesity. The situation may be different for people who got fat later. They may actually grow new fat cells — the ones they had may have become so stuffed with fat that they could hold no more.
Another question is whether fat cells removed with liposuction grow back.
Both questions are now under investigation by the Swedish researchers.
In a way, Dr. Flier noted, the discovery is a sort of back to the future moment. There was a time a few decades ago, before the current interest in how the brain regulates how much is eaten, when obesity researchers spent all their time studying and discussing fat cells. Investigators discovered that fat people had more fat cells than thin people and that fat cells shrink with weight loss and bulge with weight gain.
Dr. Jules Hirsch of Rockefeller University, who did many of the initial studies with humans, said he started because he could not understand why people who lost weight regained. “They should have been cured,” Dr. Hirsch said. After all, he said, if you cut out a fatty tumor, the fat does not grow back. Why was fat lost from dieting different?
The result was the fat cell hypothesis, a notion that obsessed researchers. Fat cells, the hypothesis said, are laid down early in life and after that, they can change only in size, not in number. When people lose weight and their fat cells shrink, that creates a signal to fill the cells again, making people regain. “We didn’t know a lot about obesity, so that was what we talked about,” Dr. Flier said.
But the discussions stalled. It was not clear what to do about those discoveries or what they meant to efforts to help people lose weight. And no one had a method to ask whether fat cells were being created and destroyed during life. Few even thought to ask that question.
That changed only recently when the new paper’s first author, Kirsty L. Spalding, a neurobiologist at the Karolinska Institute in Sweden, developed a way to ask whether new cells grow in the cortical and cerebellum regions of the human brain. She found no new cells there since birth. One day, she was giving a talk on her brain study when a scientist in the audience, Erik Arner, suggested she use the method to look at fat cells. (Dr. Arner is the second author of Dr. Spalding’s paper.) The method for dating human cells takes advantage of an effect caused by above-ground nuclear bomb testing that took place from 1955 to 1963.
When the bombs were tested, their radioactivity created a spike in the amount of a carbon isotope, C14, in the atmosphere. The C14 made its way into plants and animals that ate the plants. When people ate those plants and meat from the animals, the C14 was incorporated into their human DNA. After the nuclear test ban, C14 levels started to drop. The result is that every cell has a C14 level that reflects the level in the atmosphere at the time the cell was born.
“Each cell is a time capsule of sorts,” Dr. Spalding said.
First, the researchers confirmed that the number of fat cells remains constant in adults. Obese people who had weight loss surgery had as many fat cells two years after the surgery as before it, even though they were much thinner.
Then the investigators asked whether fat cells were being born and dying. To do that, they examined fat cells taken from 35 people, fat and lean, who had had liposuction or abdominal wall reconstruction. The amount of C14 in the cells would reveal how old the cells were. Since the number of fat cells remained constant, the number being born had to equal the number dying. And a mathematical model would reveal the dynamics of the cell turnover.
“We found the cells were really quite young,” Dr. Spalding said. “That tells us new cells are being born.”
She added: The million dollar question now is, What regulates this process? And where can we intervene?”
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