Dr. Mohit Kapoor
Dr. Mohit Kapoor, Director of the Arthritis Research Program at UHN, investigated four molecules found in the blood that contribute to cartilage degeneration. (Photo: UHN)

A research team at the Krembil Research Institute has produced new research findings which suggest that poor diet and lifestyle choices could help accelerate the speed at which knee joints degenerate as a result of osteoarthritis.

The findings, published this week in the journal Nature: Scientific Reports, show that consumption of a high fat diet leading to obesity could speed up joint degeneration. Osteoarthritis is the most common form of arthritis worldwide and it is characterized by degeneration of joint tissue, mainly cartilage, in the body's knee, spine, hand and hip joints. In Canada, more than four million Canadians are affected by osteoarthritis.

"It is already established that age and obes​ity are among the major risk factors that contribute to osteoarthritis," said Dr. Mohit Kapoor, Director of the Arthritis Research Program at UHN and Associate Professor in the Department of Surgery and the Department of Laboratory Medicine and Pathobiology at the University of Toronto.

"We also know that there is something circulating in the blood of those on a high-fat diet which causes the process to accelerate. This is what we decided to investigate."

The Krembil research team – which was led by Dr. Kapoor, postdoctoral fellow Dr. Poulami Datta and scientific associates Dr. Yue Zhang and Dr. Jason Rockel – used animal models to investigate changes to select molecules (metabolites) in the blood as a result of high-fat diet induced obesity and how these molecules contribute to cartilage degeneration in osteoarthritis.

"We identified four fat-derived molecules in the blood that are present and elevated in subjects on a high-fat diet," said Dr. Kapoor. "These are active molecules and contribute to cartilage destruction, which is the major joint tissue that is destroyed during osteoarthritis."

Progression does not slow down

In addition to pinpointing the four molecules (metabolites comprising one phosphatidylcholine and three lysophosphatidylcholines), the team also found elevated level of the hormone leptin. They found that leptin was not only elevated in the blood, but in the cartilage as well, in response to high fat diet.

The findings also show that switching to a healthy diet may have little effect on reducing the levels of these fat-derived molecules.

"The progression does not slow down," said Dr. Rockel. "Chances are, if you have an increased weight gain, even for a short period of time in your life, you may be at increased risk of osteoarthritis."

These latest results will be used to inform future research pursuits in the Arthritis Research Program at UHN.

"One of the next steps is to search for an inhibitor that could slow or block the effects of these molecules," said Dr. Datta. "We are hoping this can be delivered by injection or a pill."

In the meantime, the team is now performing additional research and testing on blood samples obtained from human patients at Toronto Western Hospital.

"These are patients that have increased BMI (body mass index) who are in the obese category. We are looking to see if these people have the elevated levels of these molecules," said Dr. Kapoor. "We don't expect these molecules to behave differently in humans."

The research published this week was funded by the Canadian Institutes of Health Research and Campaign to Cure Arthritis via the Toronto General and Western Hospital Foundation.​

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