Brüning investigates the physiological role of insulin action, particularly in the central nervous system, and the identification of the molecular mechanisms of obesity-associated insulin resistance.
In addition to the Max Planck Institute for Metabolic Research in Cologne, he is head of the Polyclinic for Diabetes, Endocrinology and Preventive Medicine at Cologne University Hospital. He led the establishment of the Cologne Cluster of Excellence on Cellular Stress Responses in Age-Related Diseases (CECAD) at the University of Cologne and was its founding director from 2007 to 2018. Since 2011 he has also led the reorientation of the Max Planck Institute to its current focus.