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

Mancini, S. J., White, A. D., Bijland, S., Rutherford, C., Graham, D. , Richter, E. A., Viollet, B., Touyz, R. M. , Palmer, T. M. and Salt, I. P. (2017) Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptorassociated kinase-4 phosphorylation. Molecular and Cellular Endocrinology, 440, pp. 44-56. (doi:10.1016/j.mce.2016.11.010) (PMID:27840174) (PMCID:PMC5228585)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mancini, Dr Sarah and Bijland, Dr Silvia and White, Dr Anna and Graham, Dr Delyth and Touyz, Professor Rhian and Salt, Dr Ian and Palmer, Dr Tim and Rutherford, Dr Claire
Authors: Mancini, S. J., White, A. D., Bijland, S., Rutherford, C., Graham, D., Richter, E. A., Viollet, B., Touyz, R. M., Palmer, T. M., and Salt, I. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Molecular and Cellular Endocrinology
Publisher:Elsevier
ISSN:0303-7207
Published Online:11 November 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Molecular and Cellular Endocrinology 440: 44-56
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
610161The role of AMP-activated protein kinase in adipocyte glucose transport and insulin signalling - utilising a knockout mouse modelIan SaltDiabetes UK (DIABETESUK)09/0003904RI CARDIOVASCULAR & MEDICAL SCIENCES
531051Regulation of inflammatory signalling in adipocytes by AMP-activated protein kinaseIan SaltDiabetes UK (DIABETESUK)09/0003948RI CARDIOVASCULAR & MEDICAL SCIENCES
580311The sensitive assessment of the activity of cellular signalling pathways regulating insulin action and the cardiovascular complications of diabetesIan SaltDiabetes UK (DIABETESUK)11/0004309RI CARDIOVASCULAR & MEDICAL SCIENCES
622511Regulation of the renin angiotension aldosterone system in adipose tissue by AMP-activated protein kinaseIan SaltDiabetes UK (DIABETESUK)13/0004652RI CARDIOVASCULAR & MEDICAL SCIENCES
587331Inhibition of vascular Stat Signalling by Amp-Activated Protein Kinase (AMPK).Timothy PalmerBritish Heart Foundation (BHF)PG/12/1/29276RI CARDIOVASCULAR & MEDICAL SCIENCES
641891Inhibition of endothelial mitogen-activated protein kinases by amp-activated protein kinaseIan SaltBritish Heart Foundation (BHF)PG/13/82/30483RI CARDIOVASCULAR & MEDICAL SCIENCES
607381Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762RI CARDIOVASCULAR & MEDICAL SCIENCES