By Laura Eggertson

When Anu Jose began reading research papers for her master’s program at Dalhousie Medicine New Brunswick, she realized a fact that struck her as unjust: scientists have traditionally conducted animal and human research on the male of the species.

“For some reason, they just ignored research with females,” she says.

As recently as 2009, for example, an article in Nature surveyed 2000 animal studies and found a male bias in 8 out of 10 biological disciplines, particularly neuroscience, pharmacy, and physiology.

Traditionally, researchers often referenced potential hormonal fluctuations in women and female animals as the reason they did not study them – a factor subsequent research has dismissed.

This underrepresentation of women, in both animal models and human studies, can result in poorer health outcomes for women.

That’s why Jose, now in her second year of a PhD program at DMNB, decided to focus on research that could improve women’s health.

She’s studying the way the metabolism affects disease progress, focusing on an enzyme called Lipid Phosphate Phosphatase 3, or LPP3. This enzyme regulates lipid metabolism in ways that benefit women’s heart health.

“This enzyme is the key to restoring cell function – as well as to reducing lipid levels, especially in females,” Jose says.

Lipids - including cholesterol or triglycerides - are fatty compounds in the membranes of cells that help with storing energy, making hormones, and absorbing vitamins. If a person’s lipid levels are too high, they can obstruct blood flow through the arteries.

In the case of heart health, a buildup of lipids in artery walls impairs cardiovascular function, increasing the risk of heart disease and stroke.

High lipid levels damage heart

Jose’s research concentrates on obesity-related cardiomyopathy, or damage to the heart muscle because of excessive lipid levels. This condition is associated with high levels of lysophosphatidic acid, or LPA, a bioactive lipid.

In a paper recently published in the American Journal of Physiology, Jose and her colleague, supervised by Dr. Petra Kinesberger, demonstrated the role LPP3 and two other enzymes play in reducing the levels of LPA and improving metabolic and cardiac function.

They tested their theory by adding and deleting LPP3 in mouse models genetically altered to have elevated levels of the lipid associated with obesity-induced cardiomyopathy.

“What we have identified so far…is that these increased levels of LPP3 were able to lower the lysophosphatidic acid [lipid] levels,” Jose says.

“Interesting, we observed a protective effect in female mice but not really in male mice. “Despite being on a high-fat diet, the females did not gain as much weight or show the same degree of metabolic dysfunction.”

The research strikes a particular chord in Jose because of her own family history of diabetes and cardiovascular disease.

“Having seen so many people affected by these conditions, I wanted to contribute to finding potential solutions through research,” she says. “This could be part of the solution, especially for improving women’s metabolic health,” she says.

Key to potential therapy

In the remaining two years of her PhD, Jose will be trying to identify the molecular and signalling pathways involved in this process, to determine exactly how and why these increased levels of LPP3 reduce the potentially dangerous lipid levels.

She theorizes that LPP3 helps cells burn energy faster – but now she wants to prove that.

Ultimately, Jose’s research highlights the potential of using LPP3 as a potential therapy or drug target to lower lipid levels in women, reducing their risk of heart disease, and particularly obesity-related cardiomyopathy.

“This enzyme is the key to restoring cell function – as well as reducing lipid levels, especially in females,” she says. “If we know the mechanism involved, developing targeted therapies becomes much more feasible.”

Jose is determined to validate her theory that LPP3 helps cells boost the way they metabolize energy.

“LPP3 could pave the way for new treatments in cardiovascular medicine,” she says.

As she conducts her research, Jose is thankful for the support she’s received through the Harry and Imogen Miller Scholarship and the Dalhousie Medicine Scholarship, which she has received twice.

“These scholarships have been instrumental in advancing my research by providing the resources necessary for me to conduct complex experiments,” she says.

Philanthropic funding is crucial if medical researchers are to make groundbreaking discoveries that lead to life-saving treatments, she adds.

“Without this financial support, many promising projects—like mine—would face significant barriers, delaying progress in addressing critical health challenges like metabolic and cardiovascular diseases.”