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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
e-ISSN
1529-2916
Journal
Nature Immunology
Quellenangaben
Volume: 18,
Issue: 6,
Pages: 654-664
Publisher
Nature Publishing Group
Publishing Place
New York
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute for Pancreatic Beta Cell Research (IPI)