myeloid cell-restricted insulin receptor deficiency protects against obesity-induced inflammation and systemic insulin resistance骨髓cell-restricted胰岛素受体缺陷预防obesity-induced炎症和系统性胰岛素抵抗.pdfVIP

Myeloid Cell-Restricted Insulin Receptor Deficiency Protects Against Obesity-Induced Inflammation and Systemic Insulin Resistance 1 1 1,2 3 1 ¨ 4 Jan Mauer , Bhagirath Chaurasia , Leona Plum , Thomas Quast , Brigitte Hampel , Matthias Bluher , 3 5 ¨ 1,2,6,7,8 Waldemar Kolanus , C. Ronald Kahn , Jens C. Bruning * 1 Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany, 2 Center of Molecular Medicine Cologne (CMMC), Cologne, Germany, 3 Molecular Immune and Cell Biology Unit, Life and Medical Science Institute (LIMES), Bonn, Germany, 4 Department of Medicine, University of Leipzig, Leipzig, Germany, 5 Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States of America, 6 Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Cologne, Germany, 7 Second Department for Internal Medicine, University Hospital of Cologne, Cologne, Germany, 8 Max Planck Institute for the Biology of Ageing, Cologne, Germany Abstract A major component of obesity-related insulin resistance is the establishment of a chronic inflammatory state with invasion of white adipose tissue by mononuclear cells. This results in the release of pro-inflammatory cytokines, which in turn leads to insulin resistance in target tissues such as skeletal muscle and liver. To determine the role of insulin action in macrophages and monocytes in obesity-associated insulin resistance, we conditionally inactivated the insulin receptor (IR) gene in myeloid lineage