Integrative Physiology And MetabolismIntegrative Physiology And Metabolism

Section Heads: Ronald Kahn M.D. and Laurie J. Goodyear Ph.D.

Other Members: Yu-Hua Tseng Ph.D. and Mary-Elizabeth Patti M.D.

The laboratories in this section focus on elucidating pathophysiological mechanisms in insulin resistance, obesity, and the development of type 2 diabetes, and determining how these conditions are modified by exercise, diet, and other factors.  The Kahn laboratory studies insulin action, insulin resistance, and the developmental control of adipose tissue, and investigates the relationship between insulin resistance, obesity, and environmental factors such as the gut microbiome.  The Tseng lab investigates the regulation of energy homeostasis, with a specific focus on the role of developmental signals in brown versus white adipose cells, the identification and characterization of progenitor/stem cells that give rise to different adipose depots, and the integration of central and peripheral controls on whole body energy homeostasis. The Goodyear lab focuses on understanding the molecular mechanisms that mediate the beneficial effects of exercise on glucose homeostasis and metabolic disease.  This includes studies investigating adaptations to skeletal muscle and adipose tissue, identification of novel exercise-regulated myokines and adipokines that have health-promoting effects, and the effects of maternal and paternal exercise on offspring metabolic health. Their studies utilize cell culture, animal models, and human volunteers to have identify novel exercise-induced myokines and adipokines that mediate the benefits of exercise on glucose homeostasis. The Patti laboratory investigates how environmental or nutritional risk factors influence gene expression and metabolic function in tissues critical for insulin sensitivity and glucose tolerance.  The Patti lab also studies risk to offspring in glucose intolerant or diabetic mothers and with the Kahn lab uses iPS cells as novel models of human type 2 diabetes. Work from all of these laboratories could lead to the discovery of new targets for the treatment of diabetes and related diseases.

Recent "Highpoints":

  • Discovered the growth factors and pathways regulating development of energy-burning brown fat, suggesting a new therapeutic approach for the treatment of obesity and related metabolic disorders. Nature 2008; NEJM 2009; Nat Med, 2013; Nat Med 2015
  • Identified how interactions between gut microbiota, peptide hormones, host genetics and diet modulate insulin signaling and the predisposition to obesity and metabolic syndrome. JCI 2015; Diabetes 2015; Cell Metab 2015

  • Discovered that diabetes can lead to alterations in other tissues, including brain and bet cells, through modification of the ER stress pathway and cholesterol synthesis. Cell Metab 2010; Nat Med 2010; PloS Biol 2013; PNAS 2014, 2015

  • Discovered that subcutaneous adipose tissue functions in exercise-induced improvements in glucose homeostasis and that the AMPK-related kinase SNARK regulates muscle mass and myocyte survival. Diabetes 2015 and J Clin Invest 2015

  • Developed iPS cells and differentiated iPS cells as models of insulin resistance and type 2 diabetes.  Cell 2013; Diabetes 2014; Endocrinol 2015; PNAS 2016; Sci Rep 2016

  • Identified mechanism by which both maternal and paternal undernutrition can lead to intergenerational risk of diabetes and obesity. PLoS Genetics 2012: Diabetes 2014; Science 2014