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    Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation

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    Publication date
    2017-01-15
    Author
    Mancini, S.J.
    White, A.D.
    Bijland, S.
    Rutherford, C.
    Graham, D.
    Richter, E.A.
    Viollet, B.
    Touyz, R.M.
    Palmer, Timothy M.
    Salt, I.P.
    Keyword
    Adipocyte; AMP-activated protein kinase; Inflammation; Signalling
    Rights
    © 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
    Peer-Reviewed
    yes
    
    Metadata
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    Abstract
    Inflammation of adipose tissue in obesity is associated with increased IL-1β, IL-6 and TNF-α secretion and proposed to contribute to insulin resistance. AMP-activated protein kinase (AMPK) regulates nutrient metabolism and is reported to have anti-inflammatory actions in adipose tissue, yet the mechanisms underlying this remain poorly characterised. The effect of AMPK activation on cytokine-stimulated proinflammatory signalling was therefore assessed in cultured adipocytes. AMPK activation inhibited IL-1β-stimulated CXCL10 secretion, associated with reduced interleukin-1 receptor associated kinase-4 (IRAK4) phosphorylation and downregulated MKK4/JNK and IKK/IκB/NFκB signalling. AMPK activation inhibited TNF-α-stimulated IKK/IκB/NFκB signalling but had no effect on JNK phosphorylation. The JAK/STAT3 pathway was also suppressed by AMPK after IL-6 stimulation and during adipogenesis. Adipose tissue from AMPKα1−/− mice exhibited increased JNK and STAT3 phosphorylation, supporting suppression of these distinct proinflammatory pathways by AMPK in vivo. The inhibition of multiple pro-inflammatory signalling pathways by AMPK may underlie the reported beneficial effects of AMPK activation in adipose tissue.
    URI
    http://hdl.handle.net/10454/10903
    Version
    Published version
    Citation
    Mancini SJ, White AD, Bijland S, Rutherford C, Graham D, Richter EA, Viollet B, Touyz RM, Palmer TM, Salt IP (2016) Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation. Molecular and Cellular Endocrinology. 440: 44-56.
    Link to publisher’s version
    http://dx.doi.org/10.1016/j.mce.2016.11.010
    Type
    Article
    Collections
    Life Sciences Publications

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