Why are women at lower risk for brain inflammation? Subcutaneous fat may hold the key

In a recent study published in Diabetes, MRI and dual-energy x-ray absorptiometry (DXA) results suggest that differences in fat distribution may play an important role in protecting premenopausal females’ brains from inflammation. 

Researchers worked with male and female mice on a high-fat diet, checking for brain inflammation while examining the amount and location of fat tissue as the mice became heavier. Obese female mice had more subcutaneous fat than males and displayed no indicators of brain inflammation until menopause, at which time the overall positioning of fat became more similar to males. 

To confirm that at least some of the differences in inflammation were explained by differences in fat distribution, the researchers operated on mice of both sexes to remove subcutaneous fat. Doing so increased brain inflammation within the female mice. 

“When we took subcutaneous fat out of the equation, all of a sudden the females’ brains start to exhibit inflammation the way that male brains do, and the females gained more visceral fat,” said Alexis M. Stranahan, PhD, neuroscientist in the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Augusta University, in coverage by the school. “It kind of shunted everything toward that other storage location.”

The study’s findings encourage scientists to look carefully for possible underlying factors that may contribute to sex differences in the medical field. 

“When people think about protection in women, their first thought is estrogen,” Stranahan said. “But we need to get beyond the kind of simplistic idea that every sex difference involves hormone differences and hormone exposure. We need to really think more deeply about the underlying mechanisms for sex differences so that we can treat them and acknowledge the role that sex plays in different clinical outcomes.”

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