Barbara Kahn, M.D. (Beth Israel Deaconess Medical Center, Endocrinology) studies the cellular and molecular mechanisms for insulin resistance in obesity and type 2 diabetes. Her work has had a major impact on understanding the critical role of the adipocyte as an endocrine organ and its role as a metabolic “factory” consuming nutrients and substrates and producing metabolites that have systemic effects on insulin action, energy balance and inflammation. She uses genomic approaches with adipose tissue from genetically engineered mice to discover novel adipocyte-associated molecules such as retinol binding protein 4 which have provided important markers and mechanisms for insulin resistance and diabetes in humans. For example, her group demonstrated that elevated retinol binding protein 4 causes insulin resistance by activating both the innate and adaptive immune systems in adipose tissue. She also showed that de novo lipogenesis in adipocytes has a major role in regulating systemic insulin sensitivity in humans and rodents. These studies focused her interest on identifying metabolites which regulate glucose-insulin homeostasis. She recently published the discovery of a novel class of lipids which are made in human tissues, correlate highly with insulin sensitivity in humans, and have anti-diabetic and anti-inflammatory effects. Her lab also established a critical role for the AMP-activated protein kinase pathway in leptin action in both the hypothalamus and peripheral tissues. In addition, in collaboration with Ben Neel, she demonstrated the importance of protein tyrosine phosphatase 1B in modulating leptin and insulin action in neural and peripheral circuits that regulate adiposity and fuel homeostasis