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Pathophysiology and Molecular Pharmacology

Shedding Light on Inflammation

Why is it that when people gain weight, they become less healthy?

Scientists have long known that increased weight promotes not only diabetes but cardiovascular disease, non-alcoholic fatty liver disease and many other chronic conditions.

Investigators in Joslin’s Section on Pathophysiology and Molecular Pharmacology study pathological mechanisms that may underlie all of these conditions. The researchers particularly seek to understand inflammation, an immune-system response that fights infection but may go awry in these chronic diseases.

Joslin’s investigations in animal models have successfully detailed connections between obesity, inflammation and type 2 diabetes, and produced a leading anti-inflammatory approach for treating diabetes. The work has centered on the family of anti-inflammatory agents known as salicylates. One member of the family is salsalate, a generic drug that is chemically similar to aspirin but easier on the stomach.

In Phase II/III clinical trials done in close collaboration with Joslin’s Section on Clinical, Behaviorial & Outcomes Research, salsalate has shown highly promising preliminary results in lowering blood glucose levels for patients with diabetes. J

oslin’s basic research also has suggested that the drug may help to guard against cardiovascular disease, and that intriguing possibility is being assessed in a separate clinical trial. Joslin’s ability to directly follow up results from animal studies with clinical trials, and then to bring findings from those trials back to tests in animal models, streamlines and empowers research efforts.

Scientists now are examining in more detail the mechanisms underlying anti-inflammatory agents such as salsalate. They also are looking at the early interactions between fat cells and white blood cells that may begin the march toward the onset of diabetes, as well as investigating the effects of weight gain in other types of tissues.

All these research projects seek to broaden and deepen our understanding of the connections between weight gain and chronic conditions—and to expand our arsenal of therapies for preventing and treating disease.