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Critical Reviews™ in Immunology
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ISSN Imprimir: 1040-8401
ISSN En Línea: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.2018026750
pages 343-365

Function of Pro-Resolving Lipid Mediator Resolvin E1 in Type 2 Diabetes

Corneliu Sima
Center for Clinical and Translational Research, The Forsyth Institute, Cambridge, MA 02142, USA; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard Medical School, Boston, MA, 02115, USA
Bruce Paster
Center for Clinical and Translational Research, The Forsyth Institute, Cambridge, MA 02142, USA; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard Medical School, Boston, MA, 02115, USA
Thomas E. Van Dyke
Center for Clinical and Translational Research, The Forsyth Institute, Cambridge, MA 02142, USA; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard Medical School, Boston, MA, 02115, USA

SINOPSIS

Programming of inflammation resolution is governed by a class of specialized pro-resolving lipid mediators (SPMs) that act in concert to modulate epithelial, endothelial, and immune cell function for restoration of homeostasis. The resolution circuits are altered in obesity and associated morbidities, including type 2 diabetes mellitus (T2D), through reduced production and/or action of SPMs, which can be rescued by therapeutic SPM delivery or up-regulation of SPM receptors. Resolvin E1 (RvE1), an eicosapentaenoic acid derivative, has potent pro-resolving and insulin-sensitizing actions mediated by BLT1 and ERV1 receptors in the vasculature and metabolic organs. Nonetheless, the RvE1-mediated increase in protective adipokines such as adiponectin in white adipose tissues, the enhancement of monocyte patrolling function in the vasculature, as well as the macrophage-clearing functions improve metabolic control in obese-prone conditions. RvE1-enhanced resolving function in obesity prevents dysbiosis of the gut microflora and increased gut permeability. These functions suggest that RE1 has therapeutic potential for immunometabolic alterations associated with T2D in patients with reduced inflammation resolving capacity. SPM profiling in individuals at risk for T2D and associated complications will help to advance personalized disease management and precision medicine.


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