Abstract:
: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 α (PPARα) driven program of oxidative metabolism. Conversely, activation of STAT6 by IL-4 improves insulin action by inhibiting the PPARα-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.
journal_name
Proc Natl Acad Sci U S Aauthors
Ricardo-Gonzalez RR,Red Eagle A,Odegaard JI,Jouihan H,Morel CR,Heredia JE,Mukundan L,Wu D,Locksley RM,Chawla Adoi
10.1073/pnas.1009152108subject
Has Abstractpub_date
2010-12-28 00:00:00pages
22617-22issue
52eissn
0027-8424issn
1091-6490pii
1009152108journal_volume
107pub_type
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