The mice fed the high-fat diet before and after surgery ended up with a body weight considered obese; mice fed the high-fat diet after surgery gained more weight than controls but were not obese.

Mice in both groups ended up with abnormal changes to their metabolism and early signs of OA. As it turns out, obesity alone wasn’t enough to damage joints; even mice that weighed less had changes in their joint tissue that showed the progression to OA. In all mice, such metabolic disturbances occurred long before mice gained a lot of weight.

 “These results argue that all you need is metabolic changes. You don’t need gross weight gain to have changes in the progression of osteoarthritis,” says Mooney. 

Next Mooney’s team will try and decipher the molecular pathways that lead from metabolic disturbances to joint damage. Mooney will also use his expertise in diabetes to see whether insulin resistance – a condition in which the tissues don’t respond to insulin well and thus can’t lower blood sugar – plays a role in damaging joints. These efforts may bring to light a potential therapy; perhaps correcting diabetes and correct insulin resistance will slow down progression to OA, says Mooney.

The link between obesity and OA is actually very complicated. Adipocytes secrete many adipokines, one of which includes leptin, which regulates metabolism and body weight. Researchers need to figure out whether leptin and its protein cousins can damage cartilage directly or whether they recruit other cells for their dirty work. When, Guilak and his team at Duke studied the full range of adipokines that fat cells produce, they discovered that many are exactly the same immune proteins that OA researchers have been studying for years, “and no one had put them together to say all of the stuff in your joints may be coming from the fat,” says Guilak.

Guilak and his team set out to different ways that fat can be dangerous. In one set of experiments the researchers wondered whether exercise could reduce inflammation from a high fat-diet.

In work that was published recently in Arthritis & Rheumatism, the team fed mice a diet that was 60 percent fats, aiming to accelerate OA and hasten obesity. (An average healthy diet should include 13 percent fat but a typical, western diet comprises about 25 percent fat intake).  Would exercise have any impact at all if mice ate a lard-rich diet that contained 60 percent fat?

As it happens, mice love to run, so the team gave some of the mice on the high-fat diet access to a running wheel; the other mice on the high fat diet didn’t run at all. All of the mice ended up obese, even mice that ran the equivalent of two miles each night. But tests on the mice that were allowed exercise showed that exercise alone slowed down the immune proteins that lead to inflammation, and reduced the severity of OA.

Guilaks’ team is now studying whether different types of fat can lead to inflammation and joint damage. In the meantime, he says that obese people can protect their joints even if they don’t lose weight. “Diet is how you are going to lose weight,” says Guilak.  “Running two miles a day for a mouse was not enough to overcome an awful diet, which is true for people too. It’s very hard to overcome the balance if you are eating that much more.”

If all of this advice to eat a low fat diet and exercise seems all too familiar, think about this, reminds Guilak: Once osteoarthritis takes hold and the bones and joints are on the path to end stage joint disease, but total joint replacement may be the only option.