TORONTO, Ontario — Obesity can be detrimental to anyone’s well-being, but studies show that men tend to develop more health issues related to obesity, such as cardiovascular disease, insulin resistance, and diabetes. This gender-driven trend has always puzzled scientists and doctors alike, but researchers from York University are finally shedding some much-needed light on the mystery. Study authors observed “striking” differences among blood vessel-building cells within the fatty tissue of male and female mice.
“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 lead study author and York Professor Tara Haas with the Faculty of Health’s School of Kinesiology and Health Science, in a university release. “We were really interested in exploring that difference because, to us, it spoke of something really fascinating happening in females that protects them.”
Prof. Haas and her team observed during an earlier study that when mice develop obesity, female rodents tend to grow significantly more new blood vessels for providing that expanding fat tissue with adequate levels of oxygen and nutrients. Males, on the other hand, actually grow fewer blood vessels in response to obesity. For this newest project, Prof. Haas and her co-authors, including York PhD student Alexandra Pislaru, Faculty of Health Assistant Professor Emilie Roudier, and former York post-doctorate student Martina Rudnicki, chose to focus specifically on the differences among endothelial cells making up the “building blocks” of these fat tissue blood vessels.
Researchers made use of software to help sort through all of the thousands of genes during this process, eventually zeroing in on the specific genes linked to blood vessel growth. This approach led to the discovery that processes associated with the proliferation of new blood vessels indeed appear higher in female mice. The male mice, on the other hand, displayed signs of processes associated with inflammation.
“It was very striking the extent of inflammation-associated processes that were prevalent in the males,” Prof. Haas recalls. “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.”
Alexandra Pislaru works in Haas’ lab and took part 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.”
Obesity differences may also have a link to aging
Study authors also took note of the behaviors among endothelial cells upon being extracted 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 from each other,” Prof. Haas explains.
Female endothelial cells were observed replicating faster, but male endothelial cells displayed greater sensitivity to inflammatory stimulus. After comparing these findings with previously published data sets, researchers discovered endothelial cells from aged male mice also displayed a more inflammatory profile in comparison to cells taken from females.
“You can’t make the assumption that both sexes are going to respond to the same series of events the same way,” Prof. Haas notes. “This isn’t just an obesity related issue — I think it’s a much broader conceptual problem that also encompasses healthy aging. 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.”
While humans and mice, of course, aren’t exactly the same when it comes to genes, the research team believes these general findings likely apply to humans as well. Moving forward, Prof. Haas wants to study the same cells from human patients.
The study is published in the journal iScience.
