No amount of dieting will alter the number of fat-hoarding cells in our bodies, research has suggested.
Scientists at the Karolinska Institute in Sweden say that the number is set during adolescence and stays the same, regardless of obesity later in life.
The journal Nature reports how they tested patients who lost huge amounts of weight, and found little change in fat cell numbers.
A UK expert said eating and exercising remained key for keeping healthy.
"It explains why it's so difficult to lose weight and to keep it off - those fat cells aren't going anywhere, and they're crying out for more"
The rising rate of obesity means that a lot of scientific attention is focused on the "adipocyte", the cell type which makes up the bulk of our bellies and waistlines.
When we are getting fatter, these cells are actually expanding in size, but experts did not know for certain whether this was the only thing happening, or whether the numbers of adipocytes could go up and down as well.
If the latter was happening, then in theory, losing weight could actually reduce the number of fat cells in the body.
The Swedish researcher first tested several hundred children, adolescents and adults of various ages and found that while fat cell numbers increased through childhood, by the time adulthood was reached, the number of cells stayed the same.
They then tested the possibility that fat cell numbers could change in extreme circumstances by taking samples of fat from patients about to undergo radical weight loss.
Some of the patients were about to undergo "gastric banding", a last resort operation designed to help very obese patients lose weight by reducing the size of the stomach.
Once the weight loss was complete, another sample of fat was taken to assess if the overall number of fat cells had decreased.
Tough to lose
The researchers found that the level of fat cells had stayed the same, and lead researcher Dr Kirsty Spalding said this finding confirmed the bad news for dieters.
"It explains why it's so difficult to lose weight and to keep it off - those fat cells aren't going anywhere, and they're crying out for more."
"I think it is premature to conclude that, by the time we are adolescents, the 'game is up' in terms of the number of fat cells we can posses"
Dr Paul Trayhurn, from the University of Liverpool, said the research represented a "firm foundation" for further studies into obesity.
"It would be nice if we could find a way to lose fat by manipulating the numbers of fat cells, but there a lot of other options higher up the queue than that - such as diet and exercise.
"The real benefit of this is that it gives us solid evidence that we can use in future research into obesity and its causes."
However, another scientist, Professor Stephen O'Rahilly, from Cambridge University, said he was unconvinced by the idea that fat cell numbers were set from adolescence.
He said: "We know that, sitting in adult fat tissue, are lots of cells that don't contain fat, but are capable of doing so if the nutritional conditions are right.
"They can almost certainly do so without dividing and therefore would not be 'counted' using this technique.
"I think it is premature to conclude that, by the time we are adolescents, the 'game is up' in terms of the number of fat cells we can possess."
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