December 2019

In individuals with obesity and type 2 diabetes a surplus of energy from too much food or increased glucose and lipids can increase tissue metabolism to damaging rates. This is much like a river overflowing its banks, where water no longer channeled in a controlled way can cause catastrophic damage by being in the wrong places. The laboratory of Fraternal Order of Eagles Diabetes Research Center member, Eric Taylor, PhD, Director of the FOEDRC Metabolomics Core Facility, recently published two papers showing how constraining glucose metabolism can lead to recovery from obesity and prevent cancer.

For glucose to be fully metabolized, it needs to be converted to a molecule called pyruvate, which is then transported to the inside of the energy-producing hub of the cell called the mitochondria and burned to extract energy. In the first study, published in the journal eLife, the Taylor lab found that inhibiting pyruvate entry into skeletal muscle mitochondria increases reliance on fat oxidation for energy production. As a result, mice with disrupted skeletal muscle mitochondrial pyruvate transport are leaner, show greater insulin sensitivity, and improved recovery from diet-induced obesity. This study highlights muscle pyruvate metabolism as a potential pathway and target to treat obesity and type 2 diabetes.

In the second study, published in the journal Cell Reports, the Taylor Lab found that blocking mitochondrial pyruvate transport in the liver decreased the ability to make a molecule called glutathione that is important for tumor formation and progression. This finding is significant because obesity and diabetes are the fastest growing cause of liver cancer, and it highlights how changing mitochondrial pyruvate metabolism may not only increase recovery from obesity but also prevent diabetes-related cancer. Dr. Taylor hopes this research will contribute to new treatments of type 2 diabetes that could also prevent cancer.