Jongsoon Lee, Ph.D.
Our laboratory has been working on identifying the molecular mechanism underlying obesity-induced inflammation and insulin resistance.
Insulin resistance (also referred to as pre-diabetes syndrome) is a condition in which certain tissues of the body—notably muscle, liver and fat—no longer respond to normal levels of insulin in the body. To compensate, the pancreatic β cells must express insulin in ever-increasing quantities. Over time, the heavy demand for insulin production causes “β-cell burnout.” The pancreas cannot produce enough insulin to overcome insulin resistance, causing the development of Type 2 Diabetes.
It has been well known that obesity is the major cause for the development of insulin resistance and Type 2 Diabetes. More than 20 percent of Americans are considered obese, and this number rises to 50 percent if people who are overweight are included in the total. About 40 percent of people who are obese eventually develop diabetes. Over the past few years, the number of people with diabetes has increased to 10 percent of the population, largely due to the epidemic of obesity. Understanding obesity on the molecular level—including intracellular signaling defects - and how obesity promotes diabetes will make it possible to design treatments to reverse insulin resistance and Type 2 Diabetes and prevent the development of the diseases.
In collaboration with Dr. Shoelson at the Joslin, we have found that inflammation plays an important role in the development of obesity-induced insulin resistance and Type 2 Diabetes. In particular, we found that the IKKβ/NF-κB pathway is activated by obesity and that inhibiting this pathway improves insulin resistance and Type 2 Diabetes in animals and humans. These observations are among the first to show that chronic subacute inflammation is an important mediator of the development of obesity-induced insulin resistance and Type 2 Diabetes.
Our laboratory’s current work focuses on determining in which tissues/cells obesity-induced inflammation occur. Although classical insulin responsive tissues including muscle, liver, β cells, and adipose tissue are important for glucose homeostasis, we believe that obesity-induced inflammation is mainly mediated by immune cells, as shown in other fields, including cancer biology and immunology. This idea has generally been embraced by other researchers in the diabetes field, who have focused in particular on adipose tissue macrophages as the main drivers of obesity-induced inflammation.
However, since insulin resistance and Type 2 Diabetes are systemic diseases, we have hypothesized further that obesity first activates systemic immune cells and that this induces local inflammation, including the activation of adipose tissue macrophages, which then promotes the development of insulin resistance. Our laboratory has been testing these hypotheses by studying how immune cells in circulation and local tissues are regulated by obesity and how this then mediates the development of obesity-induced insulin resistance in animal models as well as in human, and our accumulating experimental evidence encouragingly supports these hypotheses. We believe that our research not only shows how the fields of metabolism and immunology in insulin resistance and Type 2 Diabetes can interact, it also shows the reciprocal significance of the fields of basic and clinical science.
Jongsoon Lee, Ph.D., is an Assistant Investigator in the Section on Pathophysiology and Molecular Pharmacology at the Joslin, and an Assistant Professor of Medicine at Harvard Medical School. Dr. Lee received his BS and MS degrees from Seoul National University in Korea. He received his Ph.D. in Biochemistry from Boston University School of Medicine and postdoctoral training in the Section of Molecular and Cellular Physiology at the Joslin.
Page last updated: September 14, 2014