Dr. Scott Widenmaier: Connecting Cholesterol, Obesity and Immunometabolism

Researchers Under the Scope

When Scott Widenmaier left high school, he wasn't sure what career path he wanted to pursue.

He grew up in Alameda, Saskatchewan, and soon found work on oil rigs. But by the time he was in his early twenties, he knew it was time for a change.

"I realized that winters are just too cold to continue doing that," said Widenmaier. "I wasn't sure what I was going to do with my life, but I was interested in biology and human physiology."

In his third year as a science major at the University of Regina, he became fascinated by a lab experiment examining how neurotransmitters control heart rates. He then moved west, to graduate studies at the University of British Columbia, studying endocrinology and its role in diabetes.

"I really like the elegance of the feedback circuits," said Widenmaier, who went on to land a post-doctoral position with Dr. Gökhan Hotamisligil at Harvard University's School of Public Health.

As he discovered the emerging field of immunometabolism, Widenmaier began to see links between the way the gut and the human immune system talk to each other, especially around obesity.

"That communication to the immune systems and the metabolic systems is dysfunctional and contributes to a lot of the diseases that we see linked to obesity," said Widenmaier, who studies the way the body manages cholesterol.

That's the focus of his work at the University of Saskatchewan as an assistant professor in the College of Medicine's department of Anatomy, Physiology and Pharmacology.

"There's this transcription factor that sits in a part of the cell and it recognizes when cholesterol's too high," he said. "It changes where it goes in the cell and it regulates a response by the cell to try to prevent the cholesterol from causing damage and stress."

Widenmaier has now landed a number of awards, including the Heart and Stroke Foundation's National New Investigator Award in 2020/21. Widenmaier was also named that year's McDonald Scholar.

"We've made a lot of progress with understanding the role of NRF1 and NRF2 in the liver," he said. "We've identified some molecules that may be important for protecting cells from too much cholesterol."

In this episode, hear how this work has implications for patients with heart and stroke disease, obesity, liver disease, degenerative brain conditions, as well as various forms of cancer.

"The issue with cholesterol is that we absolutely need it, but we also need it to be exactly the right amount," said Widenmaier. "There's lots of times where that that capacity gets stretched, especially under conditions of obesity."

"What are those natural adaptive systems? If we can find out what they are, can we make them work better?"