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

卷:440

Article

Mancini, Sarah J.¹  White, Anna D.¹  Bijland, Silvia^1,7  Rutherford, Claire¹  Graham, Delyth¹  Richter, Erik A.²  Viollet, Benoit^3,4,5  Touyz, Rhian M.¹  Palmer, Timothy M.⁶  Salt, Ian P.¹ 

[1] Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland

[2] Univ Copenhagen, Sect Mol Physiol, Dept Nutr Exercise & Sports, Fac Sci, DK-1168 Copenhagen, Denmark

[3] Inst Cochin, INSERM, U1016, Paris, France

[4] CNRS, UMR8104, Paris, France

[5] Univ Paris 05, Sorbonne Paris Cite, Paris, France

[6] Univ Bradford, Sch Pharm, Bradford BD7 1DP, W Yorkshire, England

[7] Haagse Hgsk, The Hague, Netherlands

关键词: Adipocyte;    AMP-activated protein kinase;    Inflammation;    Signalling;   

DOI  :  10.1016/j.mce.2016.11.010

来源: Elsevier

【 摘 要 】

Inflammation of adipose tissue in obesity is associated with increased IL-1 beta, IL-6 and TNF-alpha 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-1 beta-stimulated CXCL10 secretion, associated with reduced interleukin-1 receptor associated kinase-4 (IRAK4) phosphorylation and downregulated MKK4/JNK and I kappa K/I kappa B/NE kappa B signalling. AMPK activation inhibited TNF-alpha-stimulated IKK/I kappa B/NF kappa B 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 AMPK alpha 1(-/-) 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. (C) 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license.

【 授权许可】

Free