Inflammation and adipose tissue macrophages in lipodystrophic mice炎症和脂肪组织巨噬细胞在小鼠lipodystrophic.pdfVIP

Inflammation and adipose tissue macrophages in lipodystrophic mice 1 2 Laura Herrero , Hagit Shapiro, Ali Nayer, Jongsoon Lee, and Steven E. Shoelson Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02115 Edited by Michael Karin, University of California, San Diego School of Medicine, La Jolla, CA, and approved November 11, 2009 (received for review May 26, 2009) Lipodystrophy and obesity are opposites in terms of a deficiency zymes. Obesity is also associated with a heightened inflammatory versus excess of adipose tissue mass, yet these conditions are state in adipose tissue (6). As adipose tissue expands during accompanied by similar metabolic consequences, including insulin periods of nutritional excess, at least two inflammatory pathways resistance, dyslipidemia, hepatic steatosis, and increased risk for are activated, the stress kinase, JNK, mediates one and the diabetes and atherosclerosis. Hepatic and myocellular steatosis likely transcription factor, NF-κB, mediates the other (7, 8). Potential contribute to metabolic dysregulation in both states. Inflammation initiators of the inflammatory activation include ER and oxida- and macrophage infiltration into adipose tissue also appear to tive stress, ceramides, and other lipids, possibly by activating toll- participate in the pathogenesis of obesity-induced insulin resistance, like receptors (TLRs) (9–12). Once activated, the downstream but their contributions to lipodystrophy-induced insulin resistance consequences include the production of proinflammatory cyto- have not been evaluated. We used aP2-nSREBP-1c transgenic (Tg)