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A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity.
Nat. Immunol. 18, 654-664 (2017)
In obesity, inflammation of white adipose tissue (AT) is associated with diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic and energy-dissipating function mediated by beige adipocytes that express the uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory mechanism of beige adipogenesis in obesity that required direct adhesive interactions between macrophages and adipocytes mediated by the integrin alpha(4) and its counter-receptor VCAM-1, respectively; expression of the latter was upregulated in obesity. This adhesive interaction reciprocally and concomitantly modulated inflammatory activation of macrophages and downregulation of UCP1 expression dependent on the kinase Erk in adipocytes. Genetic or pharmacological inactivation of the integrin alpha(4) in mice resulted in elevated expression of UCP1 and beige adipogenesis of subcutaneous AT in obesity. Our findings, established in both mouse systems and human systems, reveal a self-sustained cycle of inflammation-driven impairment of beige adipogenesis in obesity.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adipose-tissue Inflammation; Diet-induced Obesity; Insulin-resistance; Brown Fat; Macrophage Polarization; Cell Recruitment; White Adipocytes; Precursor Cells; Protein-kinase; Adult Humans
ISSN (print) / ISBN 1529-2908
Journal Nature Immunology
Quellenangaben Volume: 18, Issue: 6, Pages: 654-664
Publisher Nature Publishing Group
Publishing Place New York
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)