Why is obesity more deadly for men than women?

New research from scientists at York University is shedding light on the mechanisms underpinning why men are significantly more likely to die from obesity-related diseases compared to women. The animal study suggests inflammation-associated processes are more prevalent in the fat tissue of men.

A striking 2016 study found men were three times more likely than women to die from obesity-related diseases. The study, looking at health data from around four million people, was unable to offer any explanation as to why obese men could be more vulnerable to premature death than obese women.

For the last few years a team of researchers from York University has been trying to answer that question. In 2018 the researchers discovered female mice seemed to produce more blood vessels in new fat tissue than male mice. This increased vascularity in female fat tissue was linked with lower rates of metabolic abnormalities.

This new research zoomed in on the process even further, studying the specific endothelial cells in mice that make up the blood vessels in fat tissue. The goal was to understand what sex-based genetic differences could be detected in those cells.

The findings revealed distinct genetic differences between male and female mice, particularly in relation to genes linked with inflammation. The blood vessel cells in fat tissue from male mice displayed pro-inflammatory genetic markers that were not detected in the same cells from female mice.

“It was very striking the extent of inflammation-associated processes that were prevalent in the males,” said Tara Haas, lead researcher on the project. “Other studies have shown that when endothelial cells have that kind of inflammatory response, they’re very dysfunctional, and they don’t respond to stimuli properly.”

The mystery got even stranger when the researchers looked at the behavior of the endothelial cells in lab conditions. Removed from the body, female endothelial cells from fat tissue replicated faster than similar cells from males.

“Even when we take them out of the body where they don’t have the circulating sex hormones or other kinds of factors, male and female endothelial cells still behave very differently from each other,” Haas added.

The researchers speculate that this difference in the epigenetic characteristics of endothelial cells between males and females could explain the sex-based variations in obesity-related disease. However, it’s still unclear exactly what could be causing these fundamental cellular differences in fat tissue between male and female animals.

“This isn’t just an obesity related issue – I think it’s a much broader conceptual problem that also encompasses healthy aging,” Haas said. “One implication of our findings is that there will be situations where the treatment that is ideal for men is not going to be ideal for women and vice-versa.”

The new study was published in the journal iScience.

Source: York University

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