期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 52, 页码 22617-22622出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1009152108
关键词
insulin resistance; obesity; cytokines; liver; Th2 immunity
资金
- National Institutes of Health [DK076760, HL076746, 1DP1OD6415-1]
- American Diabetes Association
- Larry L. Hillblom Foundation
- National Research Service Award [AI066402]
- Stanford Medical Scientist Training Program
- American Heart Association
- Howard Hughes Medical Institute
Immune cells take residence in metabolic tissues, providing a framework for direct regulation of nutrient metabolism. Despite conservation of this anatomic relationship through evolution, the signals and mechanisms by which the immune system regulates nutrient homeostasis and insulin action remain poorly understood. Here, we demonstrate that the IL-4/STAT6 immune axis, a key pathway in helminth immunity and allergies, controls peripheral nutrient metabolism and insulin sensitivity. Disruption of signal transducer and activator of transcription 6 (STAT6) decreases insulin action and enhances a peroxisome proliferator-activated receptor alpha (PPAR alpha) driven program of oxidative metabolism. Conversely, activation of STAT6 by IL-4 improves insulin action by inhibiting the PPAR alpha-regulated program of nutrient catabolism and attenuating adipose tissue inflammation. These findings have thus identified an unexpected molecular link between the immune system and macronutrient metabolism, suggesting perhaps the coevolution of these pathways occurred to ensure access to glucose during times of helminth infection.
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