Predicting Osteoarthritis Severity

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High-fat diets cause lasting changes in metabolism that may predict osteoarthritis severity.
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High-fat diets can cause lasting changes in metabolism that can be detected in the blood months after returning to a normal diet.

“Obese people suffer from osteoarthritis worse than non-obese people” sounds like non-news. After all, it’s common sense that carrying more weight on your joints will lead to more pain and wear-and-tear. However, the truth is more complex than that: non-weight-bearing joints (such as the hands) also see increased rates of osteoarthritis associated with obesity, suggesting that another factor is at work.

A team of researchers, including Krembil Senior Scientist Dr. Mohit Kapoor, Drs. Poulami Datta, Yue Zhang and Jason Rockel, identified this as an important gap in understanding: "We know that there is something circulating in the blood of those on a high-fat diet that causes the process to accelerate. This is what we decided to investigate."

The researchers used an experimental model to answer important questions about the relationship between obesity and osteoarthritis. This form of arthritis is the most common, with more than three million Canadians affected. Obese individuals have an increased incidence of the disease and are 33% more likely to require joint replacement surgery.

Dr. Kapoor’s team found that the consumption of a high fat diet (leading to obesity) could speed up the effects of osteoarthritis on cartilage degradation. They then identified a set of three molecules in the blood that could be used to predict the risk of developing osteoarthritis and the risk of increased severity. These molecules, called metabolites, are related to how fat is used by the body.

While eight metabolites are known to be associated with osteoarthritis, the new findings revealed that just three were needed to predict an increased risk of osteoarthritis severity. The research team also found that a hormone known to influence hunger, fat stores, metabolite levels and more—called leptin—was increased after the high fat diet. While blood levels of leptin returned to normal after switching back to a leaner diet, leptin levels in cartilage remained high for months. “The heightened levels of leptin in the joints that we observed may be key to understanding why the risk of osteoarthritis remains high for obese individuals, even after these individuals make positive lifestyle changes and lose weight,” says Dr. Kapoor.

The team is now taking these results to the clinic: they will be collecting and analysing blood samples obtained from actual patients at Toronto Western Hospital to investigate the interplay between obesity, the metabolites that they identified and leptin in osteoarthritis.

This work was supported by the Canadian Institutes of Health Research and the Toronto General & Western Hospital Foundation.

Datta P, Zhang Y, Parousis A, Sharma A, Rossomacha E, Endisha H, Wu B, Kacprzak I, Mahomed NN, Gandhi R, Rockel JS, Kapoor M. High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature. Sci Rep. 2017 Aug 15;7(1):8205. doi: 10.1038/s41598-017-07963-6.