Males Are Genetically Programmed To Burn More Fat While Females Recycle It

Research recently published in Nature Metabolism exploring how exercise affects the body reveals another male-female difference, suggesting that when vigorously working out, males are programmed to burn more fat while females are programmed to recycle it, at least in rats. Building on the findings from the rats, the researchers are now studying over 1,500 humans to investigate what happens in humans from that starting point.
The results stem from the years-long Molecular Transducers of Physical Activity Consortium (MoTrPAC) Study investigating the molecular actions that translate vigorous movement into an array of health benefits, across over two dozen sites around the country involving over 100 scientists. The researchers found that the effects of exercise are rather extensive, affecting over 35,000 molecules, none of the tissues that were studied went unchanged. 

“Everyone knows that exercise is good for you, but no one knows exactly why,” said Joshua Adkins, a scientist at the Department of Energy’s Pacific Northwest National Laboratory and a corresponding author of a study published online May 1 in Nature Metabolism. “We don’t know what’s happening in the body that creates such great benefits.”

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18 tissue types were looked at to reveal molecular signals in both sexes that demonstrated extensive benefits from exercise such as enhanced liver function, stronger heart muscle, enriched immunity, reduced inflammation, and throughout the body the mitochondria became healthier after exercise. However, according to the researchers, the most remarkable difference between the sexes was found in the fat tissues. 

“We found that fat tissue between males and females is very different even in sedentary animals,” said Christopher Newgard, a corresponding author and director of the Duke Molecular Physiology Institute. “But then I was truly gobsmacked with how amazingly different the sex-dependent responses to exercise are. Males burn fat for energy while females preserve their fat mass. This is brought about by many differences in molecular responses lurking beneath the surface in fat from male compared to female rats. The dichotomy is truly striking.”

The differences in fat characteristics were even remarkable between rats that were sedentary, over 20,000 molecular measurements were different. Overall, the fat in female rats was healthier before and after exercise. However, among sedentary rats both sexes did share one characteristic in common, they both gained weight throughout the study. 

Even more noteworthy differences were found between the sexes in treadmill running. Male rats were able to burn fat and keep it off, while the female rats initially burned it off but regained it by the end of 8 weeks. Male rats that exercised lost fat while female rats did not, but they did not gain fat as their sedentary counterparts did. However, exercise did make the fat stores for both sexes more metabolically active and energetic with fewer signals such as those involved with obesity, and this too was more noteworthy among the male rats. 

“We saw both sexes mobilize their metabolism to get the energy they need,” said first author Gina Many. “But they get their energy in different ways. Females do so without drawing much from their fat stores, likely because those are critical to reproductive health.”

“These findings help set the landscape to understand disease risk and establish a basis for more personalized and targeted health interventions,” said Many.

“This study really opened my eyes,” said Newgard. “The differences between the sexes are much more vast than I would have anticipated. This is changing the way I am approaching other studies, including one on insulin resistance in males and females. These findings provide a road map for those experiments.”

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