A research team has pinpointed the mechanism making it much harder for women to lose weight than men, indicating a sex difference in the brain’s response to obesity medication that is not reflected in current treatment strategies. The article, “Sex difference in physical activity, energy expenditure and obesity driven by a subpopulation of hypothalamic POMC neurons,”was published in the journal Molecular Metabolism.
According to the World Health Organization (WHO), women worldwide are more likely to be obese than men, with double the obesity prevalence to men in some WHO regions. But despite clear sex differences in obesity rates, no sex distinction exists in treatments trying to tackle this public epidemic.
The team, led by researchers at the University of Aberdeen, U.K., studied the response in mouse models of obesity to physical activity and energy expenditure. It found that while obese male mice with increased appetite and reduced activity could be transformed into healthy mice through obesity drug treatment, female mice under the same conditions were not.
Researchers found the cause for this response difference in pro-opiomelanocortin (POMC) peptides, brain hormones that regulate appetite, physical activity, energy expenditure, and body weight. POMC peptides are the target of obesity medications such as lorcaserin, currently in use in the U.S.
POMC neurons perform different functions, the team reported. The subset that is modified by drugs like lorcaserin influenced appetite in both male and female mice. But its influence on physical activity and energy expenditure was only seen in male mice, not in female mice. Despite effectively modeling appetite in both genders, targeting the source of POMC in females apparently has no effective impact on physical activity and total energy expenditure.
“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,” Professor Lora Heisler, from the Rowett Institute of Nutrition and Health and study’s senior author, said in a news release.
Indeed, this research might be a first step in the direction of more personalized obesity therapies, targeting each gender differently.
