Newswise — TORONTO, January 9, 2022 — A Newly published study from York University By observing «striking» differences in the cells that make up blood vessels in the fatty tissue of male and female mice, the researchers shed light on the biological underpinnings of sex differences in obesity-related diseases.
She says men are more likely than women to develop obesity-related conditions such as cardiovascular disease, insulin resistance and diabetes. Professor Tara Haas of York Faculty of Health with the School of Kinesiology and Health Sciences.
«People have used rodent models to study obesity and obesity-related diseases like diabetes, but they’ve typically always studied male rodents because females are resistant to developing the same kinds of diseases,» says Haas. study. «We were really interested in exploring this difference because to us it was talking about something really fascinating about women that protects them.»
Haas and his team observed in a previous study. When mice become obese, females develop a large number of new blood vessels to supply oxygen and nutrients to the expanding adipose tissue, while males grow much less. In this latest study, published in iScience, Haas and his co-authors, including York PhD student Alexandra Pislaru, School of Health Assistant Professor Emilie Roudier, and former York postdoctoral student Martina Rudnicki, focused on the differences in the endothelial cells that make up. The building blocks of these blood vessels in adipose tissue.
The team used software to screen out thousands of genes to reset those associated with blood vessel enlargement. They discovered that processes associated with the proliferation of new blood vessels were elevated in female mice, whereas in males, processes associated with inflammation were elevated.
“The extent of the inflammatory-related processes common in men was striking,” Haas recalls. «Other studies have shown that when endothelial cells have this type of inflammatory response, they become very dysfunctional and do not respond properly to stimuli.»
Pislaru, who works in Haas’ lab and is one of the study’s co-authors, participated in this project as part of his thesis.
«It’s exciting to observe that female endothelial cells continue to show resistance even when stressed by a prolonged high-fat diet,» says Pislaru. «The findings from our study may help researchers better understand why obesity manifests differently in men and women.»
The researchers also studied the behavior of endothelial cells as they were removed from the body and studied them in petri dishes.
“Even when we remove them from the body in a place where they don’t have circulating sex hormones or other kinds of factors, male and female endothelial cells still behave very differently from one another,” explains Haas.
While female endothelial cells proliferated faster, male endothelial cells showed greater sensitivity to an inflammatory stimulus. Comparing with previously published datasets, the researchers also found that endothelial cells from aged male mice exhibited a more inflammatory profile than female cells.
«You can’t assume that both sexes will react to the same events in the same way,» says Haas. «This isn’t just a problem with obesity – I think it’s a much broader conceptual issue that includes healthy aging. One of the implications of our findings is that the treatment that is ideal for men will not be ideal for women, and vice versa.»
The study was funded by a grant through the Canadian Institutes of Health Research, the Canadian Natural Sciences and Engineering Research Council, and the York School of Health.
While humans and mice have different genes that can be reversed, Haas believes the overall findings will likely hold, and he is interested in examining the same cells in humans in future research.
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