It is easier for women to gain weight than men because part of the brain is "wired differently" in males and females, a study has found.
Researchers say hormones responsible for regulating appetite, physical activity and energy expenditure work differently in the sexes.
The discovery could change the way obesity is tackled through targeted medication, experts at the University of Aberdeen believe.
Working with teams from the University of Cambridge and the University of Michigan, they used a mouse model to study the sex difference in weight gain driven by differences in physical activity and energy expenditure.
During the study, researchers were able to transform obese male mice with increased appetite and reduced physical activity into lean, healthy mice, but the same transformation did not occur in the female mice.
The project was led by Professor Lora Heisler from the Rowett Institute of Nutrition and Health at the University of Aberdeen.
She said: "The World Health Organisation reports higher rates of obesity in women worldwide, reaching twice the prevalence of men in some parts of the world.
"Currently there is no difference in how obesity is treated in men and women. However, what we have discovered is that the part of the brain that has a significant influence on how we use the calories that we eat is wired differently in males and females.
"Cells in this brain region make important brain hormones called pro-opiomelanocortin (POMC) peptides that are responsible for regulating our appetite, physical activity, energy expenditure and body weight.
"What we have discovered is that not every POMC neuron performs the same function.
"While the subset targeted by obesity medication lorcaserin influences appetite in both males and female mice, in males, this subset has the added benefit of also modulating physical activity and energy expenditure.
"In female mice, this source of POMC peptides does not strongly modulate physical activity or energy expenditure.
"So, while medications targeting this source of POMC peptides may effectively reduce appetite in females, our evidence suggests that they will not tap into the signals in our brain that modulate physical activity and energy expenditure."
The research, published in the journal Molecular Metabolism, could lead to the development of new sex-specific medications.
Prof Heisler added: "More than half of people in the UK are overweight and one in four are clinically obese.
"This is an enormous percentage of the population and given the links established between obesity and serious medical illnesses including cancer, heart disease and diabetes, it is essential that we strive to find new methods to tackle this epidemic to improve our health.
"This study reveals that a sex difference in physical activity, energy expenditure and body weight is driven by a specific source of brain POMC peptides.
"This could have broad implications for medications used to combat obesity, which at present largely ignore the sex of the individual."
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