Obesity is generally considered more dangerous for men because it is linked to a higher risk of developing certain health conditions, such as heart disease, type 2 diabetes, and certain types of cancer. Men with a higher amount of abdominal fat, in particular, are at a greater risk for these conditions. Additionally, obesity can lead to lower testosterone levels in men, which can result in sexual dysfunction and other health issues.
A new York University study sheds light on the biological underpinnings of sex differences in obesity-related disease, with researchers observing “striking” differences in the cells that build blood vessels in male versus female mice’s fatty tissue.
According to York Professor Tara Haas of the Faculty of Health’s School of Kinesiology and Health Science, men are more likely than women to develop obesity-related conditions such as cardiovascular disease, insulin resistance, and diabetes.
“People have used rodent models to study obesity, and the diseases that are associated with obesity – like diabetes but they’ve typically always studied male rodents, because females are resistant to developing the same kinds of diseases,” says Haas, lead on the study. “We were really interested in exploring that difference because, to us, it spoke of something really fascinating happening in females that protects them.”
People have used rodent models to study obesity, and the diseases that are associated with obesity – like diabetes but they’ve typically always studied male rodents, because females are resistant to developing the same kinds of diseases.
Professor Tara Haas
Haas and her team observed in an earlier study that when mice become obese, females grow a lot of new blood vessels to supply the expanding fat tissue with oxygen and nutrients, whereas males grow a lot less. In this latest study published in iScience, Haas and her co-authors, including York Ph.D. student Alexandra Pislaru, Faculty of Health Assistant Professor Emilie Roudier, and former York post-doctorate student Martina Rudnicki, focused on differences in the endothelial cells that make up the building blocks of these blood vessels in fat tissue.
The researchers used software to sift through thousands of genes to find those associated with blood vessel growth. They discovered that processes associated with the proliferation of new blood vessels were high in female mice, whereas processes associated with inflammation were high in male mice.
“The extent of inflammation-associated processes that were prevalent in the males was very striking,” Haas recalls. “Other studies have shown that when endothelial cells have that kind of inflammatory response, they become very dysfunctional and do not respond properly to stimuli.”
Pislaru, who works in Haas’ lab and is a co-first author of the study, participated in this project as part of her dissertation.
“It is exciting to observe the continuing resilience that female endothelial cells display even when stressed by a long-term high-fat diet,” Pislaru says. “The findings from our study can help researchers to get a better understanding of why obesity manifests differently in men and women.”
The researchers also studied the behavior of endothelial cells after they were removed from the body and placed in petri dishes. “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,” Haas says.
Female endothelial cells replicated more quickly, whereas male endothelial cells were more sensitive to an inflammatory stimulus. When compared to previously published data sets, the researchers discovered that endothelial cells from aged male mice had a more inflammatory profile than female cells.
“You can’t assume that both sexes will react the same way to the same set of events,” Haas says. “This isn’t just an obesity issue; I believe it’s a much broader conceptual issue that also includes healthy aging. One implication of our findings is that there will be situations in which the treatment that is best for men is not best for women, and vice versa.”
The research was supported by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, and York University’s Faculty of Health. While humans and mice have different genes that may be turned up or down, Haas believes the general findings would likely apply and is interested in studying the same cells in humans in future research.
