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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shen, Shudan Zhang, Chunyan Mortimer, Joanne Riggs, Arthur D. Priceman, Saul J. Lee, Heehyoung Kujawski, Maciej Kruper, Laura Yu, Hua Cherryholmes, Gregory A. Jove, Richard |
| Description | Author Affiliation: Priceman SJ ( Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, Duarte, CA 91010, USA.); |
| Abstract | Dysregulated inflammation in adipose tissue, marked by increased proinflammatory T-cell accumulation and reduced regulatory T cells (Tregs), contributes to obesity-associated insulin resistance. The molecular mechanisms underlying T-cell-mediated inflammation in adipose tissue remain largely unknown, however. Here we show a crucial role for signal transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin resistance. Stat3 activity is elevated in obese VAT and in VAT-resident T cells. Functional ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and glucose tolerance, and suppresses VAT inflammation. Importantly, Stat3 ablation reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to elevated IL-6 production, leading in turn to suppression of Tregs. In addition, Stat3 in T cells in DIO mice affects adipose tissue macrophage accumulation and M2 phenotype. Our study identifies Stat3 in VAT-resident T cells as an important mediator and direct target for regulating adipose tissue inflammation, DIO, and its associated metabolic dysfunctions. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 32 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Insulin Resistance Immunology Intra-Abdominal Fat Obesity STAT3 Transcription Factor T-Lymphocyte Subsets Animals Blood Glucose Metabolism Blotting, Western Diet, High-Fat Adverse Effects Fasting Blood Flow Cytometry Inflammation Genetics Insulin Interferon-gamma Interleukin-6 Pathology Macrophages Mice Mice, Inbred C57BL Mice, Knockout Etiology Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Regulatory Th1 Cells Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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