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 Salt, Dr Ian and Palmer, Dr Timothy and Graham, Dr Delyth and Rutherford, Dr Claire and Touyz, Professor Rhian |
| 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 > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| 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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